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Unlabelled: We performed a 3-year longitudinal study of a group of 179 healthy Chinese adolescents (92 boys and 87 girls) aged from 12 to 16 years to determine the effects of puberty, physical activity, physical fitness, and calcium intake on the acquisition of bone mass. At yearly intervals for 3 consecutive years we recorded nutrition, calcium intake and anthropometric measurements, and assessed pubertal status according to Tanner. Bone mass of the lumbar spine was determined by dual-energy X-ray absorptiometry and radial bone mass by single-photon absorptiometry. Physical fitness and level of physical activity were assessed and muscle strength and power determined by isokinetic testing. Peripheral bone mass correlated with axial skeleton bone mass. Age, pubertal staging, physical fitness and muscle strength were significantly associated with bone mass increments on cross-sectional univariate and regression analysis. Longitudinal regression analysis showed that the most important factor affecting bone mass accretion in adolescents in both sexes was their pubertal stage. In boys, bone mass increment throughout the study was greater in children who were already in the advanced pubertal stages on entering the study than in those who started puberty in year 2 or 3 of the study. The percentage change in bone mineral content of the forearm and in bone mineral density of the lumbar spine was greater than 25% in the advanced pubertal group as compared to around 20% in the less mature group. For girls, the reverse was true. The increment of bone mass during the study period was significantly greater in those who presented in the earlier pubertal stages than in those who were at the more advanced stage of puberty on entry into the study. There was no significant effect of calcium intake and physical activities on the bone mass accretion., Conclusion: In Chinese adolescents, bone mineral accretion at adolescence is not influenced by exercise, level of physical fitness and calcium intake. In both sexes, and especially in girls, to optimally increase bone mass, regular physical exercise programmes should be instituted well before the onset of puberty rather than at or after it. Once puberty starts, these interventions may have no or only limited effect.

Objective: The objectives were to estimate the prevalence and correlates of physical abuse-related outcomes in the family setting in Hong Kong's adolescent population., Method: A cross-sectional study design was used. A randomly selected sample of 3,355 secondary school students in Kwai Tsing District of Hong Kong was surveyed. The response rate was 98%., Results: The prevalence rates of corporal punishment, being beaten by parents for no apparent reason, being beaten to injury by family members in the past 3 months and any one of the above three were 4.9% (95% CI, 4.2% to 5.6%), 2.0% (95% CI, 1.5% to 2.5%), 1.1% (95% CI, .98% to 1.2%) and 6.6% (95% CI, 5.7% to 7.5%), respectively. Students who had experienced the above physical abuse-related outcomes were at a significant disadvantage for a wide range of morbidity indicators, including self-perceived bad health, anxiety and stress, somatic illnesses (such as asthma and epigastric pain), injuries and accidents, and hospitalization. They were more likely to have poor familial relations and coping skills, and to take up habits which potentially put their health at risk, such as smoking, alcohol consumption, and fighting with others., Conclusions: Our prevalence estimates of physical abuse in the family setting for a student population in Hong Kong is an improvement over previous local estimates of physical abuse occurrence, which were mainly based on case notifications and clinical samples. The results also show that the abused adolescents are growing up in an environment filled with physical, psychological, and familial adversities.

The activity of beta-galactoside alpha2,6-sialyltransferase (ST6Gal.1), the enzyme responsible for the addition of sialic acid in alpha2,6-linkage to N-acetyllactosaminic (Gal beta1,4GlcNAc) units of glycoconjugates, is increased in the vast majority of colon cancer specimens, and a positive correlation with an invasive phenotype has been suggested by several studies. In many tissues, ST6Gal.1 is regulated mainly at the transcriptional level through the use of different cell-specific promoters which generate transcripts differing in their 5'-untranslated regions. With the aim of understanding the molecular bases of the increased ST6Gal.1 expression in colon cancer, we investigated the expression of mRNA species in colon cancer cell lines and the relationship with enzyme activity and extent of alpha2,6-sialylation of cell glycoproteins. All cell lines examined express the form containing the 5'-untranslated exons Y and Z, typical of the "basal" expression of the gene, while others express also the liver transcript. This indicates that colon cancer cell lines can be grouped according to expression of the liver transcript of ST6Gal.1. The cell lines expressing only the Y+Z form display, in general, a lower activity:mRNA ratio, which might indicate reduced translational efficiency. The level of alpha2,6-sialylation of cell glycoproteins, as determined by reactivity with the Sambucus nigra lectin, is closely associated with the level of enzyme activity.

Sialoglycans on the cell surface of human colon cancer (HCC) cells have been implicated in cellular adhesion and metastasis. To clarify the role of N-acetylneuraminic acid (NeuAc) linked alpha2,3 to galactose (Gal) on the surface of HCC cells, we studied the intercellular adhesion of HCC cell lines expressing increasing NeuAcalpha2,3Gal-R. Our model system consisted of the HCC SW48 cell line, which inherently possesses low levels of cell surface alpha2,3 and alpha2,6 sialoglycans. To generate SW48 clonal variants with elevated cell surface NeuAcalpha2,3Gal-R linkages, we transfected the expression vector, pcDNA3, containing either rat liver cDNA encoding Galbeta1,3(4)GlcNAc alpha2,3 sialyltransferase (ST3Gal III) or human placental cDNA encoding Galbeta1,3GalNAc/Galbeta1,4GlcNAc alpha2,3 sialyltransferase (ST3Gal IV) into SW48 cells. Selection of neomycin-resistant clones (600 microgram G418/ml) having a higher percentage of cells expressing NeuAcalpha2,3Gal-R (up to 85% positive Maackia amurenis agglutinin staining compared with 30% for wild type cells) was performed. These ST3Gal III and ST3Gal IV clonal variants demonstrated increased adherence to IL-1beta-activated human umbilical vein endothelial cells (HUVEC) (up to 90% adherent cells compared with 63% for wild type cells). Interestingly, ST3Gal III and ST3Gal IV clonal variants also bound non-activated HUVEC up to 4-fold more effectively than wild type cells. Cell surface NeuAcalpha2,3Gal-R expression within the various SW48 clonal variants correlated directly with increased adhesion to HUVEC (r=0.84). Using HCC HT-29 cells, which express high levels of surface NeuAcalpha2,3Gal-R, addition of synthetic sialyl, sulfo or GalNAc Lewis X structures were found to specifically inhibit intercellular adhesion. At 1.0mM, NeuAcalpha2,3Galbeta1,3(Fucalpha1, 4)GlcNAc-OH and Galbeta1,4(Fucalpha1,3)GlcNAcbeta1,6(SE-6Galbeta1++ +, 3)GalNAcalpha1-O-methyl inhibited HT-29 cell adhesion to IL-1beta-stimulated HUVEC by 100% and 68%, respectively. GalNAcbeta1, 4(Fucalpha1,3)GlcNAcbeta1-O-methyl and GalNAcbeta1,4(Fucalpha1, 3)GlcNAcbeta1,6Manalpha1,6Manbeta1-0-C30H61, however, did not possess inhibitory activity. In conclusion, these studies demonstrated that cell surface NeuAcalpha2,3Gal-R expression is involved in HCC cellular adhesion to HUVEC. These specific carbohydrate-mediated intercellular adhesive events may play an important role in tumor angiogenesis, metastasis and growth control., (Copyright 1999 Academic Press.)

Tarsal tunnel syndrome is an uncommon clinical entity. This article will review the published reports on tarsal tunnel syndrome with respect to its anatomy, cause, pathophysiology, clinical presentation, diagnosis, treatment, and results of treatment in an attempt to improve understanding of this problem.

Announcements of public interests (APIs) on television (TV) have been an important means of AIDS prevention. Recently in Hong Kong, the first API on TV which was communicated by a male AIDS patient, named J.J., was displayed on the screen from April to December, 1995. The objective of this study is to examine the effectiveness of this API, as compared with other APIs previously shown in Hong Kong. Collecting data from a random sample of 1,275 residential respondents in Hong Kong through a telephone survey, this study demonstrated that the public gave very favorable evaluation on J.J.'s API, when compared with other APIs. Remarkable impacts of J.J.'s API on the public included increasing concern for AIDS, condom use, and testing blood for HIV infection, and reducing the number of sex partners. The impacts tended to be more salient on male than female viewers. Some of these impacts also appeared to vary by different levels of education and family income.

An in vitro study was performed on 11 cadaver legs to study the effects of tarsal tunnel release, distraction calcaneocuboid arthrodesis, and triple arthrodesis on tibial nerve tension in surgically created pes planus feet. Baseline tibial nerve tension was measured during maximal dorsiflexion, eversion, combined dorsiflexion-eversion, and cyclical load with varying degrees of internal rotation. These measurements were repeated on the same leg after each surgical procedure. This study demonstrated that a tarsal tunnel release significantly increased nerve tension during eversion, dorsiflexion-eversion, and cyclical load compared with the pes planus foot. Both triple arthrodesis and distraction calcaneocuboid arthrodesis were effective at decreasing tibial nerve tension; the former was more effective than the latter. Procedures producing skeletal instability, such as ligament release producing a pes planus deformity and a tarsal tunnel release, increased tibial nerve tension. Procedures that corrected deformity and increased stability decreased tibial nerve tension. If increased tibial nerve tension plays a role in the pathophysiology of tarsal tunnel syndrome, then this needs to be considered for treatment of patients with this syndrome.

Objective: To determine the relation of puberty, physical activity, physical fitness, and calcium intake with bone mineral content (BMC) of the distal radius, and on bone mineral density (BMD) of the L2 to L4 vertebrae in a group of healthy Chinese adolescents., Design: Cross sectional survey., Subjects: A group of 179 healthy Chinese adolescents (92 boys and 87 girls) aged 12 to 13 years enrolled in the first year of the Tii Junior High School in Shatin, Hong Kong. Ninety four of the pupils enrolled were in the physical education major class (PE), and the other 85 were in the art major class (ARTS)., Main Outcome Measures: Correlation of BMC of the distal radius and BMD of the L2 to L4 vertebrae with level of physical activity, physical fitness (isometric and isokinetic), muscle strength of the upper and lower limb, and calcium intake., Results: BMC of the distal radius and BMD of the L2 to L4 vertebrae were significantly positively correlated. Univariate and regression analysis showed that age, pubertal staging, physical fitness, and muscle strength were significantly associated with bone mass in a positive way. Calcium intake and type of sport practised did not exert a significant influence on BMC of the distal radius and BMD of the L2 to L4 vertebrae in boys. The results for the BMD of the L2 to L4 vertebrae were similar in girls and boys; however, in girls, the BMC of the distal radius had a negative correlation with calcium intake. Physical fitness was a significant positive predictor of BMD of the L2 to L4 vertebrae., Conclusions: Among Chinese adolescents bone mass was positively influenced by certain measures of physical fitness as well as by age, weight, and pubertal stage.

The ranges of sodium and potassium intake and their relationship to blood pressure were studied in 126 healthy Chinese subjects (42 men, 84 women) aged between 20 and 65 years living in Hong Kong. An average of three blood pressure measurements and one to three 24-hour urinary sodium and potassium outputs were used to characterize an individual's blood pressure, and sodium and potassium intake, respectively. The average sodium and potassium intakes were 145 and 40 mmol/day in men and 135 and 41 mmol/day in women. When compared with subjects of similar age in southern China, Chinese in Hong Kong excreted 20% less sodium but 40% more potassium and had a lower systolic blood pressure (113 vs 118 mmHg in men, 106 vs 112 mmHg in women). It should be remembered that the Hong Kong subjects were heavier and were under more urban stress, both of which would be expected to be associated with higher blood pressure. The findings from this pilot study are compatible with a positive association between sodium intake and blood pressure and/or an inverse association between potassium intake and blood pressure.

Patients with tarsal tunnel syndrome of unknown etiology do poorly after surgical decompression. Although surgical decompression addresses the soft tissue constraints, it ignores the role of osseous support. Some authors have suggested that a pes planus deformity (i.e., valgus hindfoot and abducted forefoot) is an unrecognized cause of tarsal tunnel syndrome due to increased tibial nerve tension. An in vitro study was performed on nine cadaveric feet to determine the effects of foot position and load on tibial nerve tension. Tensile forces placed through the tibial nerve were measured when the foot was placed in dorsiflexion, eversion, combined dorsiflexion-eversion, and then under cyclical load and increasing internal rotation at 5 degrees increments from 0 degrees to 20 degrees. The nerve tension was reassessed after the creation of a pes planus deformity under the previous conditions. Tibial nerve tension in the stable and unstable foot was significantly increased by eversion, dorsiflexion, and combined dorsiflexion-eversion. Tibial nerve tension was significantly greater in an unstable foot when compared with a stable foot during eversion, dorsiflexion, and combined dorsiflexion-eversion. In the stable foot, tibial nerve tension was significantly increased during axial loading with increasing internal rotation when compared with 0 degrees rotation. The increased tibial nerve tension in the stable foot was significant with increasing internal rotation when 0 degrees was compared with 10 degrees, 15 degrees, and 20 degrees. In the unstable foot, the tibial nerve tension was significantly increased with increasing internal rotation compared with the nerve tension at 0 degrees of rotation. The increased tibial nerve tension in the unstable foot was significant with increasing internal rotation when 0 degrees was compared with 5 degrees, 10 degrees, 15 degrees, and 20 degrees. When stability of the foot and internal rotation were compared independently, each factor increased tibial nerve tension. However, these factors acting together did not significantly compound the increase in nerve tension. This study demonstrates that tibial nerve tension is increased in an unstable foot compared with a stable foot during eversion, dorsiflexion, combined dorsiflexion-eversion, and cyclical load with increasing internal rotation.

Background: Stigmata of hemorrhage predict rebleeding and outcome of patients with bleeding peptic ulcers. There are variabilities in reported incidences of stigmata and their respective rebleeding risks. We sought to study the interobserver agreement among experts., Methods: Between June 1994 and July 1994, 100 consecutive patients with bleeding peptic ulcers underwent videoendoscopy within 24 hours of their admissions. An edited videotape of these ulcers was compiled and sent to an international panel of 14 experts. They independently rated these ulcers exclusively into one of the six categories: spurting, oozing, nonbleeding visible vessel, adherent clot, flat pigmented spot, or clean based. Agreement between any two experts was expressed by a kappa estimate (kappa). Agreements over individual stigmata and a composite kappa estimate (kappa(w)) signifying overall agreement were also computed., Results: Out of the possible 91 pairwise kappa estimates among 14 experts, 35 (38.5%) were less than or equal to 0.40, indicating poor agreement. None of the kappa estimates was greater than 0.75. Composite kappa estimates for individual stigmata were as follows: spurting kappa = 0.664, oozing kappa = 0.420, nonbleeding visible vessel kappa = 0.342, adherent clot kappa = 0.426, flat pigmented spot kappa = 0.393, and clean-based ulcer kappa = 0.371. The weighted kappa estimate was 0.426., Conclusion: Agreement between experts was poor in more than a third of occasions. Although the overall interobserver agreement was fair (0.4 < kappa < 0.75), agreements for nonbleeding visible vessels, flat pigmented spots, and clean-based ulcers were poor.

The extent of processing of N-linked oligosaccharides and the sialylation of the target cell membranes has been positively correlated with resistance to lysis mediated by NK cells, but a conclusive evidence has never been reached. Colon cancer tissues express an increased activity of beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, alpha 2,6ST), which catalyzed the addition of sialic acid in alpha 2,6-linkage to Gal beta 1,4GlcNAc (N-acetyllactosamine) sequences of glycoprotein N-linked chains. The resulting increased level of membrane alpha 2,6-sialylation appears to be related with a more invasive behavior of cancer cells. This phenomenon may depend on a decreased sensitivity of colon cancer cells to NK cells. To obtain conclusive evidence on the role played by sialylation of N-linked chains in determining the target cell susceptibility to NK-mediated lysis, human colon cancer cell lines not expressing sialyltransferases acting on N-linked chains were transfected with a rat alpha 2,6ST cDNA. Stable transfectants expressed different levels of alpha 2,6ST activity, were reactive with the Sambucus nigra lectin, specific for alpha 2,6-linked sialic acid, and compared with control transfectants, showed a remarkable decrease in the number of unsubstituted Gal beta 1,4GlcNAc terminal sequences. The NK susceptibility of these clones was found to be identical to that of control transfectants, either when unstimulated- or IL-2-stimulated lymphocytes were used as effectors. Neuraminidase treatment of target cells does not result in significant changes to NK susceptibility. Our data demonstrate that sialic acid alpha 2,6-linked to N-linked chains of target cell glycoproteins does not play a major role in recognition of the target by human NK cells.

ST6Gal I (beta-galactoside alpha 2,6-sialyltransferase, SiaT-1, ST6N, EC 2.4.99.1) mediates the attachment of the alpha 2,6-sialyl linkage common on N-linked glycans. Previous work suggests substantial inter-species conservation in SIAT1, the gene encoding ST6Gal I. In human and in rat, hepatic-specific SIAT1 transcription is initiated at Exon I. Here we report a surprising departure in the structural organization of the murine ST6Gal I gene. By a combination of primer extension analysis, 5'-RACE analysis, and analysis of genomic sequences, we show that the murine hepatic ST6Gal I mRNA contains a novel region 5' of Exon I. This novel sequence is encoded on a discrete upstream exon, Exon H. In contrast to human and rat hepatic ST6Gal I, the murine mRNA is transcriptionally initiated at the start of Exon H. Differential mRNA blot analysis indicates that transcripts containing Exon H sequences are preferentially expressed in liver.

Multiple mRNA isoforms are generated from SIAT1, the gene encoding the beta-galactoside alpha 2,6-sialyltransferase (ST6Gal I, SiaT-1, ST6N, alpha 2,6ST). These isoforms are transcriptionally initiated from a number of physically distinct promoter regions. In human B-lymphocytic cells, two SIAT1 mRNA isoforms have been identified. In order to determine if additional SIAT1 mRNA isotypes exist, RNA from Louckes, a human cell line with the mature B-phenotype, was subjected to 5'-RACE analysis. In addition to the two previously characterized mRNA forms, three additional SIAT1 mRNA forms were identified. The new mRNA isoforms incorporate novel sequence blocks into their 5'-UT regions. The data strongly suggest that these novel sequence blocks originate from previously undocumented 5'-noncoding exons and are incorporated into mRNA by alternative splicing events and/or usage of additional transcriptional promoter regions. BLAST analysis reveals no similarity of these novel regions, Exons U, V, and W, to sequences in GenBank. The only exception is Exon V, which contains a portion of Alu, a repetitive element. The data suggest that two of these novel mRNA isotypes are likely to be minor components. However, one form may contribute significantly to the SIAT1 mRNA pool in Louckes cells.

Purpose: To establish the prevalence and severity of myopia among the Chinese Hong Kong students and to study the relationship between myopia and optical components., Methods: One thousand and seventy-five freshmen of the 1993-1994 academic year in the Chinese University of Hong Kong underwent the eye examination including evaluation of refractive error, keratometry, and A-scan ultrasonic biometry. The data were analyzed with the SPSS/PC+4.01 statistical package., Results: The prevalence of myopia was 91.7% with the mean refraction being -4.00 +/- 2.64D in this young adult population. The statistical analyses demonstrated a significant correlation between refractive value and axial length of the globe (r = -0.78), vitreous length (r = -0.76), anterior chamber depth (r = -0.33), lens thickness (r = 0.13) and corneal curvature (r = 0.19)., Conclusion: The refractive status is mainly dependent on the axial length. In general, the higher the myopia was, the longer the eyeball, the deeper the anterior chamber, the steeper the cornea, and the thinner the lens would be.

The relationship between upper gastrointestinal hemorrhage and drug use was studied in 251 Chinese patients (179 men, 72 women) admitted to the Prince of Wales Hospital, Hong Kong, and control subjects matched for age and sex. There was a highly significant difference between the cases and control subjects in the use of NSAIDs (odds ratio 14.0, p < 0.00001), ulcer healing drugs (odds ratio 12.5, p < 0.00001), and Chinese proprietary medicines (odds ratio 16.0, p < 0.00001). There was also a significant difference in the use of analgesics (odds ratio 14.0, p = 0.001), paracetamol (odds ratio 2.5, p = 0.01), antacids (odds ratio 2.7, p < 0.001) and unknown drugs (odds ratio 4.7, p < 0.001). Cases also differed from control subjects regarding the use of tobacco (odds ratio 2.3, p < 0.001) and alcohol (odds ratio 1.7, p = 0.02), and the presence of peptic ulcer symptoms (odds ratio 29.8, p < 0.00001). Significantly more control subjects than cases were receiving aspirin, cardiovascular drugs, bronchodilators, oral hypoglycemic drugs/lipid-lowering drugs, and anticonvulsants/hypnotics, due to the inevitable differences in disease pattern between the 2 groups. NSAID use was a major factor associated with upper gastrointestinal hemorrhage from primarily peptic ulcers. Differences in the use of other drugs may reflect variations in disease patterns between cases and controls, the common practice of self-medication in Hong Kong, and the concomitant use of NSAIDs and ulcer healing drugs/antacids.

To identify the risk factors for developing recurrent ulcer complications after recovery from an episode of peptic ulcer bleeding 611 patients admitted with peptic ulcer bleeding were studied. Some 557 (91 per cent) were discharged without operation. A total of 22 patients were lost to follow-up and five were excluded as maintenance H2 blockers were required. Of the remaining 530 patients at risk, 169 (32 per cent) developed another complication (166 bleeding, three perforations) over a median follow-up period of 36 months. Patients with duodenal ulcers at the time of bleeding, previous history of peptic ulcer, previous bleeding, history of dyspepsia longer than 3 months, and a short interval between previous ulcer complications and the index bleed were more likely to develop further complications. Sex, age, smoking, coexisting illness, non-steroidal anti-inflammatory drugs intake and time taken to achieve ulcer healing had no predictive value.

A single human gene, SIAT1, encodes the beta-galactoside alpha 2,6-sialyltransferase from which multiple mRNA isoforms are generated. In rat, expression of the hepatic mRNA isoform (Form 1) has been defined with respect to the transcriptional initiation site and promoter region. We show here that a similar hepatic SIAT1 mRNA isoform exists in human. Another human mRNA isoform, a mature B-cell-specific mRNA isoform (Form 2), was previously reported. Here, we used 5'-RACE and S1 nuclease protection analysis to define the 5'-untranslated region of Form 2 human SIAT1 mRNA. We demonstrate conclusively that Form 2 mRNA is initiated from a point completely distinct from that of Form 1 mRNA. A number of cis-acting regulatory elements residing immediately 5'of the Form 2 initiation site includes AP-1, AP-2, NF-kappa B, NF-IL6, C/EBP, and CREB. A TATAA box is also present 29 bp 5' of the transcriptional initiation site. CAT reporter gene expression from serially-truncated segments of the 5'-flanking region of the Form 2 initiation site indicates that the segment between -784 and +125 was sufficient to promote high level CAT expression in Louckes, a mature B-cell line. The 5'-flanking region to the human Form 1 initiation site is competent in expression of CAT upon transfection of the fusion construct into HepG2, a human hepatoma cell line. Cellular specificity of expression is apparently retained. Louckes cells expressed CAT efficiently from Form 2 promoter but only marginally from the Form 1 promoter. In contrast, CAT expression from Form 1 promoter is more efficient than from the Form 2 promoter in HepG2 cells.

We have previously documented a dramatic elevation in the activity of alpha 2,6-sialytransferase towards Gal beta 1,4GlcNAc (EC 2.4.99.1) (alpha 2,6ST) in CaCo-2 cells maintained in culture for several days after confluence to elicit a high degree of enterocytic differentiation phenotype. Northern analysis performed with a probe complementary to a region of human alpha 2,6ST mRNA common to all known transcripts demonstrated that the expression of alpha 2,6ST mRNA in CaCo-2 cells increased with the degree with the degree of differentiation. When probes complementary to 5'-untranslated exons (Y + Z or X) previously identified in transcripts isolated from human placenta and from several human lymphoblastoid cell lines were used, no hybridization signal with mRNA of CaCo-2 cells was found, as reported for the mRNA of hepatoma cell line HepG2 (Wang XC, Vertino A, Eddy RL, Byers MG, Jani-Sait SN, Shows TB, Lau JTY (1993) J Biol Chem 268: 4355-61). These results support the notion that the major alpha 2,6ST transcript of CaCo-2 cells was the hepatoma isoform or a new one, so far unreported. Consistent with the differentiation-dependent increase in alpha 2,6ST-mRNA expression, an elevation of the reactivity with Sambucus nigra agglutinin of differentiated CaCo-2 cell-surface was observed, indicating an enhanced alpha 2,6-sialylation of membrane glycoconjugates.

Lipoprotein(a) (Lp(a)) is an independent marker of cardiovascular disease which is relatively unresponsive to treatment with most of the commonly prescribed lipid lowering drugs. Concentrations of Lp(a) increase after the menopause, and the primary aim of this study was to determine whether combined hormone replacement therapy was effective in lowering levels of Lp(a) in postmenopausal women. An open longitudinal study was conducted among 42 women who had undergone a spontaneous menopause and were attending the outpatient clinic of the Prince of Wales Hospital, Hong Kong. All subjects were treated with 2 mg oral estradiol daily and 5 mg medroxyprogesterone acetate for 12 days each calendar month. Fasting blood samples for lipoprotein measurement were taken before the commencement of treatment and at 6 and 12 months. Lp(a) levels showed a skewed distribution with a median value before treatment of 9.45 mg/dl (range 1.47-95.62 mg/dl). After 6 months, there was a reduction to 7.70 mg/dl (1.12-72.59 mg/dl) (P < 0.01), and after 12 months the median concentration was 7.14 mg/dl (0.63-69.23 mg/dl) (P < 0.001 0-12 months). There were also significant reductions in the concentrations of apo B from 116.13 to 111.62 mg/dl and LDL-C from 3.02 to 2.74 mmol/l (P < 0.05), plus a lowering of TC of borderline significance. Apo A-I increased from 162.56 to 173.35 mg/dl (P < 0.01), but there were no significant changes in HDL-C or the HDL-C subfractions. TC, LDL-C, apo B and TG concentrations were higher and HDL-C and HDL2-C concentrations were lower when blood was sampled during combined treatment with estrogen and progesterone than when estrogen was being taken alone. Levels of Lp(a) were also lower during the estrogen only phase of treatment, but none of these differences were statistically significant. This study demonstrates that combined cyclical hormone replacement therapy is effective in reducing concentrations of Lp(a). The trend towards a more atherogenic lipid profile during the combined phase of treatment suggests that attention should be given to the timing of blood sampling in future studies of this nature.

A role of alpha 2,6-linked sialic acid in the development of an invasive phenotype in colon cancer has been suggested by several observations but never conclusively demonstrated. An experimental model to clarify this tissue was established by the creation and characterization of a bank of cell lines that differ mainly, if not exclusively, in the degree of alpha 2,6-sialylation. Human colon cancer cell lines SW48 and SW948, normally unable to elaborate the alpha 2,6-sialyl linkage, were transfected with the beta-galactoside alpha 2,6-sialyltransferase (alpha 2,6ST) cDNA driven by the cytomegaloviral promoter and screened for cell surface alpha 2,6-sialylated sugar chains using fluorescein isothiocyanate-conjugated Sambucus nigra agglutinin (SNA-FITC). A panel of SNA-FITC-positive clones was established that expresses alpha 2,6ST activity of varying degrees. Only the SNA-FITC-positive recombinants express the 1.2 Kb mRNA predicted to be generated from the transfected sequence. No 4.3-4.7 Kb transcripts that are indicative of transcription from the native alpha 2,6ST gene were detected.

The synthesis of alpha 2,3-linked sialic acid to Gal(beta 1,3)GalNAc is mediated by at least three beta-galactoside alpha 2,3-sialyltransferases (EC 2.4.99.4, SiaT-4) that are encoded by three distinct genes. In contrast, only a single gene encodes the beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, SiaT-1). This report assesses the relationship and nature of the SiaT-4 genes. Analysis of human-mouse somatic cell hybrids demonstrates that the sialyltransferase genes are dispersed in the human genome. The gene for SiaT-4 resides in chromosome 8, that for SiaT-4b resides in p21-p34 of chromosome 1 and that for SiaT-4c in q23.3-qter of chromosome 11. The gene symbols for these genes have been designated SIAT4A, SIAT4B and SIAT4C, respectively. To assess the structural organization of one of the SiaT-4 genes, a human SiaT-4a cDNA from submaxillary glands was isolated and characterized. Rapid amplification of cDNA 5' ends (5'-RACE) analysis indicates an unusually long 1 kb 5'-untranslated leader. The catalytic domain of the cloned sequence was expressed in transfected cells and was shown to be competent in mediating the specific synthesis of sialic acid alpha 2,3 to Gal(beta 1,3)GalNAc-R. Genomic sequences for SiaT-4a were also isolated and examined. The data demonstrate that coding information for SiaT-4a protein is dispersed into seven discrete exon segments in a manner reminiscent of the SiaT-1 gene. Furthermore, as in the SiaT-1 gene, intervening sequences interrupt both sialylmotif domains, regions that are conserved among all known sialyltransferases.

1. To determine if the risk of aspiration is increased in 'Dettol' (4.8% chloroxylenol, pine oil and isopropyl alcohol) poisoning and the factors that may be responsible, a study was made of 89 patients and 89 matched control subjects with other forms of poisoning admitted to the Prince of Wales Hospital, Hong Kong. 2. Aspiration was more common in patients with Dettol poisoning (8% vs 3%, P = 0.16). There were more control subjects with drowsiness at presentation (54% vs 24%, P < 0.0001), but the use of gastric lavage (88% vs 64%, P < 0.001) and the occurrence of vomiting (62% vs 17%, P < 0.0001) were more common in patients with Dettol poisoning. 3. Our findings suggest that Dettol poisoning may be associated with an increased risk of aspiration. This increase in risk may be related to the use of gastric lavage and the common occurrence of vomiting in patients with Dettol poisoning.

A striking biochemical alteration to the epithelium of the small intestine upon weaning is the loss of microvillar sialic acids. Antibody and cDNA probes to the beta-galactoside alpha 2,6-sialyltransferase (SiaT-1, EC 2.4.99.1) were used to characterize the expression of this sialyltransferase in the small intestine of suckling rats. SiaT-1 mRNA and protein in the intestinal epithelium are rapidly lost upon weaning, in agreement with the loss of mucosal sialic acids and general sialyltransferase activity. Developmental repression of SiaT-1 is manifested in a proximal to distal gradient; SiaT-1 mRNA and protein are lost first from the duodenum and persist the longest in the ileum. We have previously documented that SiaT-1 gene expression can be transcriptionally initiated from a number of distinct tissue-specific promoter regions. Here, by criteria of mRNA mobility on agarose gels, primer extension analysis, and differential Northern hybridization, we show that the promoter previously considered to be liver-specific is operative in SiaT-1 expression in the small intestine of suckling animals. Comparison of this SiaT-1 promoter region with promoter regions of other genes exhibiting dual intestine-hepatic tissue specificity revealed a number of striking sequence similarities. Regulatory implications and consequences of small intestinal SiaT-1 expression in suckling but not in weaned animals are discussed.

Pretreatment neck node biopsy had been performed on 50 of 422 patients who had cervical node metastases from nasopharyngeal carcinoma when initially seen. Multivariate analysis using the Cox proportional hazards model shows that pretreatment node biopsy is not a significant determinant of distant metastases, survival, or recurrence in the neck. Results of similar studies are reviewed and the role of pretreatment node biopsy in nasopharyngeal carcinoma discussed.

The human beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1) (SiaT-1) gene is localized to human chromosome 3 (q21-q28) by Southern analysis of somatic cell hybrids and by in situ hybridization of metaphase chromosomes. Comparative analysis between the human and the previously reported rat SiaT-1 genomic sequences demonstrates precise conservation of the intron/exon boundaries throughout the coding domains. Furthermore, there is extensive inter-species sequence similarity in some of the exons that contain information only for the 5'-leader regions. Human genomic sequences were also analyzed to reconcile reported differences in the 5'-untranslated region in SiaT-1 mRNAs. In cultured cell lines of the B-lineage, Reh, Nalm-6, Jok-1, Ball-1, Daudi, and Louckes, the study demonstrates that three upstream exons, Exons(Y+Z) and Exon(X), are mutually exclusively utilized, resulting in at least two distinct populations of SiaT-1 mRNA being synthesized. None of these exons is present in the SiaT-1 mRNA isotype expressed in HepG2 human hepatoma cells. In all B-lymphoblastoid cell lines examined, the basal level SiaT-1 mRNA is maintained by the expression of an isotype containing the Exons(Y+Z) sequence. The slightly smaller SiaT-1 mRNA, which contains the Exon(X) sequence but not Exons(Y+Z) sequence, is synthesized at a high level and found only in Jok-1, Daudi, and Louckes, the cell lines with mature B-cell phenotype. The study also provides further evidence that induced SiaT-1 expression accompanies the appearance of CDw75, a putatively sialylated cell surface epitope and a marker of human mature B-lymphocytes. The SiaT-1 induction is the result of the appearance of a novel form of SiaT-1 mRNA isotype.

The present study, utilizing the hormone-responsive rat thyroid cell line FRTL-5, presents evidence establishing the regulatory role of thyrotropin in modulating mRNA for beta-galactoside alpha 2,6-sialytransferase, the enzyme responsible for the expression of alpha 2,6-linked sialic acid. Both the cell surface membrane and the thyroglobulin secreted by cells grown in the presence of this hormone exhibit a marked decrease in the level of alpha 2,6-bound sialic acid with little or no change in the number of alpha 2,3-sialic acid residues. An additional, and unexpected, sequel is the finding of a coordinated decrease in all of the core monosaccharide constituents of the secreted thyroglobulin. Both of the above phenomenological changes appear to be at some variance with previously described systems wherein thyrotropin was deemed to increase glycosylation. It is anticipated that further resolution of this apparent difference may provide a clearer definition for the role of the carbohydrate moiety in affecting the biological function of thyroglobulin.

A large-scale community survey in Shatin, Hong Kong, is presented with a modified two-phase design using flagged and nonflagged subsamples. A modified Self-Reporting Questionnaire and the Diagnostic Interview Schedule (version III) were used as the screening and diagnostic instruments, respectively. Lifetime rates for 19 Diagnostic Interview Schedule/DSM-III diagnoses are presented. The most common diagnoses in Shatin were tobacco dependence, generalized anxiety disorder, alcohol abuse and/or dependence, all phobias, and dysthymic disorder. The male-predominant disorders were tobacco dependence, alcohol abuse/dependence, pathological gambling, and antisocial personality. The female-predominant disorders were generalized anxiety disorder, all phobias, dysthymic disorder, major depressive disorder, obsessive-compulsive disorder, and bereavement.

The psychiatric morbidity among 718 Chinese primary school children from a lower middle social class area in Hong Kong was studied, using a two-stage design. The screening procedures included two parts, a multi-component scale and a battery of probing questions. The screening procedures achieved an overall sensitivity of 75% and a specificity of 97%. The findings on prevalence were: (i) a total prevalence of all definite psychiatric cases of 16.3%; (ii) prevalence according to diagnostic categories: emotional disorder, 8.8%; conduct disorder, 2.0%; mixed disturbance of emotion and conduct, 3.0%; hyperkinetic syndrome, 1.0%; hyperkinetic conduct disorder, 1.0%; and Gilles de la Tourette's syndrome, 0.4%; (iii) boys 2.7 times more affected than girls; (iv) emotional disorder much more common than conduct disorder, even in boys; and (v) the prevalence of borderline cases was 19.5%. The mean duration of morbidity for all definite cases was 41.7 months. About half of all definite cases were seriously impaired in one or more areas of functioning and the other half moderately impaired. These results were compared with findings obtained from studies done in other countries.

beta-Galactoside alpha 2,6-sialyltransferase (SiaT-1), like other glycosyltransferases, is differentially expressed in rat tissues. Two distinct size classes of SiaT-1 mRNAs expressed in rat kidney are comprised of at least three SiaT-1 transcripts. One mRNA, RKE, represents the larger transcript class (4.7 kb) and predicts a polypeptide identical to the hepatic SiaT-1. In transfected Chinese hamster ovary (CHO) cells, RKE polypeptides exhibit hemi-perinuclear staining with a SiaT-1 antibody (Ab-267) that is consistent with Golgi localization. RKE transfectants display cell-surface alpha 2,6-sialic acid linkages as determined by lectin affinity staining. Two other mRNAs, RKA and RKB, are members of a smaller size class (3.6 kb) that comprise predominant SiaT-1 transcripts in rat kidney. Both RKA and RKB encode polypeptides that are missing the amino-terminal 232 residues, but retain 171 amino acids of RKE carboxy-terminal sequence information. A short, leucine-rich peptide present in the divergent amino-terminus of RKA has sequence similarity to the secretory signal domain of several eukaryotic secretory and cell-surface proteins. In transfected CHO cells, both RKA and RKB polypeptides display an immunostaining pattern that is distinct from that of the Golgi-associated SiaT-1 protein (RKE). Furthermore, RKA or RKB transfectants do not display alpha 2,6-sialic acid linkages on cell-surface glycoconjugates. Consistent with the expression of divergent SiaT-1 mRNAs in rat kidney, protein blot analysis of rat tissue homogenates with Ab-267 reveals that in addition to protein that co-migrates with hepatic SiaT-1, rat kidney expresses a unique size class of SiaT-1 proteins.

n-Butyrate, a short chain fatty acid that is produced by colonic bacterial fermentation, is detectable in portal blood and induces differentiation in various human neoplastic cell lines. Earlier reports indicated approximately 20-fold induction in vitro by n-butyrate of the sialyltransferase that catalyzes terminal glycosylation of GM3 ganglioside in HeLa and colon cancer cells. We previously isolated a 1.3-kilobase cDNA for a human beta-galactoside alpha 2,6-sialyltransferase, for which N-linked glycoproteins are the acceptors. We report here that treatment of Hep G2 cells with 5 mM n-butyrate for 24 h reduced beta-galactoside alpha 2,6-sialyltransferase mRNA levels by approximately 90%. Reductions in mRNA level were followed by approximately 75 and approximately 90% reductions, respectively, in specific beta-galactoside alpha 2,6-sialyltransferase enzyme activity after treatment for 24 and 36 h with 5 mM n-butyrate. However, in contrast with earlier reports of enhanced ganglioside synthesis in response to n-butyrate treatment, incubation of Hep G2 cells with n-butyrate did not alter the ganglioside pattern as assessed by thin layer chromatography of lipids extracted from treated cells. Nuclear run-on reactions indicated that the rate of transcription of beta-galactoside, alpha 2,6-sialyltransferase was not altered by treatment with 5 mM n-butyrate for 24 h, but the effects of this treatment on cytoplasmic levels of beta-galactoside alpha 2,6-sialyltransferase mRNA were largely negated by co-treatment with actinomycin D or cycloheximide. Therefore, our results show that n-butyrate reduces expression of mature beta-galactoside alpha 2,6-sialyltransferase mRNA by post-transcriptional mechanisms.

The level of serum-soluble interleukin-2 receptor (sIL-2R) was measured in 32 patients to investigate the effect of prednisone and alpha-interferon therapy on chronic hepatitis B virus infection. All the patients were seropositive for hepatitis B surface antigen and hepatitis B e antigen, with histological evidence of chronic persistent or chronic active hepatitis. Twenty-six patients received oral prednisone, followed by subcutaneous recombinant alpha-interferon, and six patients received multivitamin tablets and served as controls. After 4 wk of prednisone in reducing dosage, serum sIL-2R fell significantly from 673.6 +/- 52.9 U/ml to 584.8 +/- 39.4 U/ml (mean +/- SE, p less than 0.05). It rose to 733.4 +/- 45.7 U/ml (p less than 0.05) on the 4th wk of interferon, but returned to pretreatment level at completion of interferon. There was a significant correlation between serum sIL-2R and alanine aminotransferase levels (r = 0.36, p less than 0.001). The level of serum sIL-2R before treatment and its response to prednisone and interferon were not useful in predicting seroconversion of hepatitis B e antigen and anti-hepatitis B e.

The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially utilized by liver and kidney in the generation of mRNAs that predict substantially divergent polypeptides. In order to determine the biosynthetic relationship between these sialyltransferase mRNA isoforms, genomic sequences were isolated and analysed. Five exons that span at least 40 kb of DNA carry the coding information for the liver beta-galactoside alpha 2,6-sialyltransferase protein. An additional exon contains only sequences for the 5'-untranslated leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this gene share only three coding exons that specify the carboxyl terminal 42% of the liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain information from two other exons that comprise the 5' divergent region of these transcripts. Primer extension and S1 nuclease protection analysis demonstrate that the hepatic and kidney specific mRNAs are transcriptionally initiated at different sites within the sialyltransferase gene. While the hepatic sialyltransferase mRNAs are transcribed from the first exon, the kidney transcripts are initiated from a site within the third intron. Genomic regions upstream of both transcriptional initiation sites can regulate expression of the bacterial chloramphenicol acetyltransferase gene in transiently transfected L cells. Together, the data implicate multiple promoters as a principle mechanism in the generation of kidney and liver gene product diversity in sialyltransferase expression.

The growth of the splenic remnant after partial splenectomy and autogenous splenic implants was compared in immature rats. Implants placed in the subcutaneous pouch of the anterior abdominal wall and the retroperitoneal space had none or minimal regeneration. Splenulus formed in the omental wrap were small, multiple and the combined weight was less than the original graft tissue, and more ectopic splenulus and intra-abdominal adhesions were formed. Splenic remnants after three-quarter splenectomy with an intact blood supply grew to 30-46% of the weight of the spleen of the control; and increased in size as the animal matured.

The problem of diagnosis of peptic ulcer in children was analysed in a series of 50 consecutive cases. Atypical symptomatology occurred frequently and resulted in errors in diagnosis in six instances: perforated ulcer was misdiagnosed as appendicitis in five and bleeding ulcer was misdiagnosed as Meckel's diverticulitis in one. Barium meal was the investigation employed in earlier years but had proven unsatisfactory, being incorrect in four out of 22 examinations. Fiberoptic endoscopy was introduced in recent years and having achieved correct diagnosis in 20 patients with no errors, has established itself as the choice of investigation.

The beta-galactoside alpha-2,6-sialyltransferase represents a member of a family of sialyltransferases which catalyze the terminal addition of sialic acid to maturing carbohydrate chains. We surveyed rat tissues using cDNA probes complementary to coding and noncoding domains of the rat liver alpha-2,6-sialyltransferase. In addition to the expected differences in the level of sialyltransferase mRNA among the tissues, there were dramatic qualitative differences as well. Hepatic sialyltransferase probes hybridize to mRNAs of varying size on Northern blots. A tissue-dependent pattern of expression of these transcripts is documented. Evidence is presented that the multiple transcripts are generated from a common gene sequence. At least one instance of alternate splicing in the generation of the kidney sialyltransferase transcripts is predicted by S1 nuclease analysis. We report the isolation of a rat kidney cDNA clone, RKA, that substantiates this tissue-specific alternate splicing event. The RKA insert, although less than full-length, apparently encodes a polypeptide divergent from the reported hepatic alpha-2,6-sialyltransferase (1). RNA blot analysis indicates that the RKA-type transcripts represent a significant proportion of sialyltransferase RNA in rat kidney. Another class of kidney cDNA clones, RKE, is colinear with the hepatic sialyltransferase sequence. RNA blots probed for the divergent and common regions suggest that complex processing pathways are operative in the tissue-specific expression of sialyltransferase mRNA.

The biosynthesis of galactosyl-beta 1,3-N-acetylglucosamine has been demonstrated using membrane preparations from pig trachea. Unlike the UDP-galactose:2-acetamido-2-deoxy-D-glucose 4 beta-galactosyltransferase, which is inhibited by high levels of N-acetylglucosamine, the UDP-galactose:N-acetylglucosamine 3 beta-galactosyltransferase shows no inhibition at 200 mM N-acetylglucosamine. About 80% of the total disaccharide synthesized at 200 mM N-acetylglucosamine was base-labile suggesting the 1,3-linkage, alpha-Lactalbumin inhibits galactose incorporation into galactosyl-beta 1,4-N-acetylglucosamine but has little or no effect on the activity of the 1,3-galactosyltransferase. Escherichia coli beta-galactosidase readily hydrolyzed the base-stable product, but not the base-labile component. The apparent 1,3-linked disaccharide was reduced with NaBH4 and was isolated by Bio-Gel P-2 column chromatography. Methylation analysis by gas chromatography/mass spectrometry showed tetramethyl galactose and a 3-substituted N-acetylglucosaminitol. Neither the beta 1,4 nor the beta 1,3 disaccharide was hydrolyzed by green coffee bean alpha-galactosidase. Both disaccharides were readily hydrolyzed by bovine testes beta-galactosidase. This is the first report on the galactosyltransferase which catalyzes the synthesis of the galactosyl-beta 1,3-N-acetylglucosamine linkage such as found in the Type I chain of human blood group substances. A tissue survey in rats showed only rat intestine to have readily detectable UDP-galactose: N-acetylglucosamine 3 beta-galactosyltransferase activity. The intestinal membrane fraction like the tracheal enzyme catalyzes the synthesis of two disaccharides as judged by base treatment, and these appear to be the beta 1,3 and beta 1,4 isomers of galactosyl-N-acetylglucosamine.

The value of adjunctive penile block for analgesia, after circumcision in children using 0.5 percent bupivacaine has been evaluated in this randomized, prospective trial. Significantly more children without nerve block were found to require analgesics, administered by injection orally, in the first 12 hour period when compared with children given the nerve block. Penile block is a procedure that is safe, simple to achieve, free from complications, and covers the postoperative period when analgesia is much needed.

Two mongoloid patients with Hirschsprung's disease are presented. Mongoloid children who have severe constipation should be investigated for Hirschsprung's disease.

The apparent cure rate of infants with biliary atresia is compared before and after the introduction of the Kasai-type procedure. While the operation has been criticized for many of its postoperative problems, it still compares favourably in terms of the apparent cure rate, i.e. an improvement from 4.5% to 35.3%.

Synthesis of alpha- and beta-tubulin is controlled in animal cells by a novel autoregulatory mechanism: the concentration of unpolymerized subunits specifies the level of tubulin mRNAs. Using transient DNA transfection, we have localized the sequences that identify a beta-tubulin RNA as a substrate for autoregulation. Insertion of as few as 106 nucleotides (57 bases of 5' untranslated region and 49 coding nucleotides) from a beta-tubulin gene into a thymidine kinase gene is sufficient to make expression of the resultant chimeric RNA regulated as if it were an authentic beta-tubulin mRNA. Furthermore, all 5' untranslated region sequences can be deleted without disrupting regulation. We conclude that this novel autoregulatory pathway is specified by cytoplasmic events that modulate mRNA stability through sequences lying within the first 16 translated codons of a beta-tubulin mRNA.

Nucleotide pyrophosphatase, a Zn2+-dependent enzyme catalyzing the hydrolysis of sugar nucleotides, generally interferes with glycosyltransferase assays. Certain tissues such as intestinal mucosa are particularly rich sources of nucleotide pyrophosphatase activity. The inhibition of nucleotide pyrophosphatase without affecting glycosyltransferase activities by the removal of Zn2+ allows for the assay of galactosyltransferases in rat intestinal particulate fractions. Inactivation of nucleotide pyrophosphatase was achieved by preincubation of particulate enzyme preparations in the presence of EDTA. Addition of Mn2+, required for the galactosyltransferase assays, did not reactivate the nucleotide pyrophosphatase. The presence of 0.05% (w/v) soybean trypsin inhibitor was required during the preparation of intestinal mucosa homogenates and enzyme assays to protect the UDP-galactose: N-acetylglucosaminyl galactosyltransferase from inactivation.