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Biomedical subjects

S Ho

Publications and source records attributed to S Ho.

At least 109 records · Page 6Linked to original sources
PubMed1995

Sodium fluoride dissolution of human calcium oxalate/phosphate stone particles.

The dissolutive effects of sodium fluoride on human calcium stone particles were investigated in an in vitro model. Stone particles composed of 65% calcium oxalate and 35% calcium phosphate dissolved in a dose-dependent fashion with NaF exposure. Stone particles exposed to 60 mM NaF had a 17% reduction in particle mass after 24 hours and a 62% reduction after 7 days in comparison with experimental controls bathed in physiologic normal saline. The systemic toxicity of the dose of oral fluoride necessary to achieve the optimal tested urinary concentrations would likely preclude oral administration, but NaF may have an adjunctive role in upper urinary tract irrigation for residual stone fragments after lithotripsy or in chronic low-dose oral administration for prophylaxis against recurrent calcium nephrolithiasis.

Administration, Oral↗
PubMed1994

A surrogate 15 kDa JC kappa protein is expressed in combination with mu heavy chain by human B cell precursors.

A novel kappa protein, encoded by a germline JC kappa transcript, is expressed by normal and leukemic human B cell precursors. The transcript displays an open reading frame initiated by a non-AUG codon, and predicts a 15 kDa molecule which could be readily confirmed by in vitro translation. Cellular expression was demonstrated by immunofluorescence, precipitation and Western blotting. Furthermore, 2-D gel electrophoresis revealed that germline JC kappa can covalently associate with mu heavy chain at the surface of pre-B cells. We therefore propose that during B cell lymphopoiesis, two alternative pathways could be operative in which mu heavy chain can either associate with lambda 5 or germ-line JC kappa.

Amino Acid Sequence↗
PubMed1994

Growth inhibitory and agonistic signals of interleukin-7 (IL-7) can be mediated through the CDw127 IL-7 receptor.

The present study was aimed at identifying surface-membrane molecules involved in the regulation of human B-cell ontogeny. For this purpose, murine monoclonal antibodies (MoAbs) were generated against Pre-Alp, a pre-B acute lymphoblastic leukemia (ALL) cell line, and MoAb R34.34 was selected for further characterization. R34.34 recognized a molecule expressed on normal B-cell precursors (BCP) but not on mature B cells. The antibody also reacted with T lymphocytes, a subpopulation of monocytes from peripheral blood, and a subset of CD34+ cells. Immunoprecipitation analysis indicated that R34.34 recognizes an 80-kD molecular weight antigen. Antibody R34.34 was further found to be directed against an epitope interfering with binding of interleukin-7 (IL-7) to Pre-Alp cells. Expression cloning from a Pre-Alp cDNA library showed that R34.34 antigen is CDw127, the 75- to 80-kD IL-7 receptor. Proliferation of the B-lineage ALL cell lines Reh and Mieliki was inhibited by IL-7, and this effect was specifically reverted by MoAb R34.34. In addition, antibody R34.34 specifically inhibited IL-7-dependent proliferation of normal BCP, Pre-Alp cells, and peripheral T cells. These results imply that both inhibitory and proliferative effects of IL-7 can be mediated through the same receptor on various lineages. R34.34 antibody should be important for the analysis of signal transduction through CDw127.

Adult↗
PubMed1994

A set of endoplasmic reticulum proteins possessing properties of molecular chaperones includes Ca(2+)-binding proteins and members of the thioredoxin superfamily.

The major proteins in the lumen of the endoplasmic reticulum (ER) are thought to function in Ca2+ sequestration or as "molecular chaperones" in the folding and assembly of membrane or secreted proteins. Based on the ability of many chaperones to bind selectively to unfolded proteins and to dissociate from them upon ATP hydrolysis, we developed an affinity chromatography method to isolate proteins with these characteristics from pancreatic or liver ER. Seven ER proteins bound selectively to denatured protein columns and were specifically eluted by ATP (10(-6) M) but not by a nonhydrolyzable ATP analog. These proteins were identified with antibodies and microsequencing as the ER chaperone BiP (grp78), grp94, calreticulin, a novel 46-kDa protein that binds azido-ATP, as well as three members of the thioredoxin superfamily: protein-disulfide isomerase, ERp72, and a previously reported 50-kDa protein (p50). This set of seven proteins bound to and was eluted with ATP from a variety of denatured proteins, including histone, gelatin, alpha fetoprotein, thyroglobulin, lysozyme, casein, and IgG. The release of grp94, protein-disulfide isomerase, ERp72, calreticulin, and p50 was stimulated by Ca2+ in the presence of ATP. These proteins thus appear to function as Ca(2+)-dependent chaperones, which may account for the Ca2+ and ATP requirement for protein folding in the ER.

Adenosine Triphosphate↗
PubMed1994

Crystal structures of cyclophilin A complexed with cyclosporin A and N-methyl-4-[(E)-2-butenyl]-4,4-dimethylthreonine cyclosporin A.

BACKGROUND: Cyclophilin (CyP) is a ubiquitious intracellular protein that binds the immunosuppressive drug cyclosporin A (CsA). CyP-CsA forms a ternary complex with calcineurin and thereby inhibits T-cell activation. CyP also has enzymatic activity, catalyzing the cis-trans isomerization of peptidyl-prolyl amide bonds. RESULTS: We have determined the structure of human cyclophilin A (CyPA) complexed with CsA to 2.1 A resolution. We also report here the structure of CyPA complexed with an analog of CsA, CsA (MeBm2t1-CsA), which binds less well to CyPA, but has increased immunosuppressive activity. Comparison of these structures with previously determined structures of unligated CyPA and CyPA complexed with a candidate substrate for the isomerase activity, the dipeptide AlaPro, reveals that subtle conformational changes occur in both CsA and CyPA on complex formation. CONCLUSIONS: MeBm2t1-CsA binds to CyPA in an essentially similar manner to CsA. The 100-fold weaker affinity of its binding may be attributable to the close contact between MeBmt1 and the active site residue Ala103 of CyPA, which causes small conformational changes in both protein and drug. One change, the slight movement of MeLeu6 in CsA relative to MeBm2t1-CsA, may be at least partially responsible for the higher affinity of the CyPA-MeBm2t1-CsA complex for calcineurin. Our comparison between CyPA-CsA and CyPA-AlaPro suggests that CsA is probably not an analog of the natural substrate, confirming that the catalytic activity of CyPA is not related to its role in immunosuppression either structurally or functionally.

Amino Acid Isomerases↗
PubMed1994

Cloning and characterization of NF-ATc and NF-ATp: the cytoplasmic components of NF-AT.

Present evidence indicates a pathway of signal transmission in T cells that is outlined in figure 1. The elevation in intracellular calcium that is induced by interactions at the antigen receptor leads to the activation of the calcium-dependent phosphatase calcineurin. This in turn leads to the nuclear association of the cytosolic component of NF-ATc. The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins. Once in the nucleus, NF-ATc interacts with NF-ATn to form an active transcriptional complex. NF-ATn is a ubiquitous protein, can be synthesized in response to PMA, and has many similarities to AP-1. The mechanism by which NF-ATc enters the nucleus is unknown, and although it appears to require calcineurin, NF-ATc has not yet been shown to be an in vivo substrate of calcineurin. Alternative mechanisms include the possibility that NF-ATc operates on some cytoplasmic anchor or that other proteins that are controlled by calcineurin carry out the nuclear import of NF-ATc. Although NF-ATp copurifies with NF-ATc, there is as yet no understanding of how NF-ATp is functioning in vivo. Now that these proteins are purified and cloned, the major goals will be to understand their role and the roles of other family members in thymic development.

Animals↗
PubMed1994

Cardiovascular causes of loss of consciousness in patients with presumed epilepsy: a cause of the increased sudden death rate in people with epilepsy?

UNLABELLED: BACKGROUND, METHODS, AND RESULTS: Syncope and seizures are often indistinguishable clinically. We present a series of 12 patients diagnosed as having epilepsy. Despite normal or nonspecific electroencephalographic findings, 11 of 12 patients were treated or offered treatment with long-term anticonvulsant agents. Subsequently, diagnoses of arrhythmic or neurally mediated syncope were made in all patients using Holter monitoring, long-term ambulatory loop electrocardiographic recording, or tilt-table studies. Arrhythmias included torsades de pointes (four patients), atrioventricular nodal reentrant supraventricular tachycardia (one patient), and sinus arrest (two patients). The remaining five patients had neurally mediated syncope with hypotension and bradycardia, including asystole in two patients. Treatment for the documented cardiovascular abnormalities resulted in the alleviation of syncopal symptoms. CONCLUSIONS: Because the observed cardiovascular abnormalities are potentially fatal, this series suggests that undiagnosed cardiac syncope may contribute to the documented increased sudden death rate in patients with presumed epilepsy. Cardiac causes of loss of consciousness should be considered in patients with presumed epilepsy, atypical premonitory symptoms (such as nausea, lightheadedness, or palpitations), nondiagnostic electroencephalograms, and failure to respond to anticonvulsant therapy.

Adolescent↗
PubMed1994

Cytoreductive surgery for hepatocellular carcinoma.

A prospective study was conducted on 26 patients for cytoreductive surgery of inoperable hepatocellular carcinoma. These patients underwent cytoreduction with liver resection, cryosurgery, microwave tissue coagulation and/or absolute alcohol injection. In-hospital mortality was 7.7%. The symptomatic relief and quality of survival were excellent. The median survival of patients after cytoreduction was 10.0 months and the survival was much better than those of 26 patients matched by sex, age, tumour size, Child-Pugh grading and Karnofsky scores who received systemic chemotherapy during the same period of the study (log rank test, P = 0.0001). There was no statistical difference between the survival curves of those patients who received (19 patients) and those who did not receive (7 patients) additional treatment by chemotherapy or selective internal radiation therapy after cytoreduction. This suggests that the gained survival benefit could have been derived mainly from the cytoreductive surgery rather than the additional treatments.

Adolescent↗
PubMed1994

Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study.

Eighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-to-normal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy. The treatment was given through an arterial port placed during laparotomy. The radiation doses to the liver and tumour were determined intraoperatively with a beta probe and liquid scintillation counting of multiple liver biopsies. The treatment was well tolerated without major complications. In all patients the tumour marker fell to a level which ranged from 41% to 0.2% of the pretreatment level. Tumour regression was found to be dose related. Progressive or static disease occurred in a higher proportion of patients whose tumours received < 120 Gy (P = 0.005). Survival was better in those whose tumours received > 120 Gy (median survival = 55.9 weeks) than those whose tumours received lower doses (median survival = 26.2 weeks). This difference is statistically significant with P = 0.005. We conclude that yttrium-90 microsphere therapy is safe and that tumour response is dose related. A tumour dose of > 120 Gy is recommended.

Adolescent↗
PubMed1994

A cancer attitude survey among medical undergraduates in Hong Kong.

A cancer attitude survey was administered to a cohort of 152 final-year medical undergraduates in Hong Kong from mid-1988 to mid-1990, on the first and last days of a four-week oncology module. Significant differences in pre- and post-module scores suggest that the course had significant impact on attitudes toward early diagnosis, treatment aggressiveness, and acceptance of death. The changes are generally regarded by the teachers as desirable. Comparison with a similar survey performed ten years earlier on a group of American second-year medical undergraduates shows significant differences in most of the pre-course scores. Factor analysis shows that the items in the survey could not be readily categorized by a limited number of factors, thus casting doubt on the validity of the instrument in reflecting attitudinal attributes as described in the original survey.

Attitude to Death↗
PubMed1994

Diagnostic pharmaco-scintigraphy with hepatic intra-arterial technetium-99m macroaggregated albumin in the determination of tumour to non-tumour uptake ratio in hepatocellular carcinoma.

Between October 1990 and March 1993, 124 patients who had hepatocellular carcinoma (HCC) underwent diagnostic pharmaco-scintigraphy with hepatic intraarterial technetium-99m macroaggregated albumin (TcMAA) to determine the tumourous to non-tumourous liver tissue uptake ratio (T/N ratio). There were 110 males and 14 females. Ages ranged from 16 to 73 with a median of 55 years. The range of T/N ratio was 0.7 to 19.3 with a median of 3.8. 12 patients with inoperable HCC were subsequently selected by predetermined criteria to undergo treatment with hepatic intraarterial yttrium-90 microspheres and the T/N ratios in these patients were validated by beta probe dosimetry and liquid scintillation count of multiple liver biopsies. The T/N ratio determined by preoperative diagnostic TcMAA scan correlated well with intraoperative beta probe dosimetry, with coefficient of correlation r = 0.82. Preoperative TcMAA scan also correlated well with liquid scintillation count of biopsy specimens, with r = 0.96. We conclude that TcMAA scan can be used to determine the T/N ratio in patients with HCC, thus allowing better selection of patients with inoperable tumours for loco-regional therapy.

Adolescent↗
PubMed1994

Selective internal radiation therapy with intra-arterial iodine-131-Lipiodol in inoperable hepatocellular carcinoma.

UNLABELLED: From August 1990 to June 1993, 26 patients with inoperable hepatocellular carcinoma were treated with intra-arterial iodine-131-Lipiodol (131I-L). METHODS: Iodine-131-Lipiodol was given through either an implantable arterial port (9 patients) or during hepatic angiography (17 patients). All 26 patients had multiple lesions, 3 had involved resection margin after surgical resection and 1 had diffuse infiltrative lesions. The median size of the largest tumor among 22 patients with a measurable lesion was 4.5 cm (2-9.5 cm). The end points are tumor response in terms of tumor size, change in serum alpha-fetoprotein level, toxicity of treatment and overall survival. RESULTS: Twenty-three patients received a single treatment of 1.11-2.22 GBq (30-60 mCi)131I-L. Three patients received 2.22-4.44 GBq (60-120 mCi)131I-L in three fractions. Considering both radiological regression and reduction in serum alpha-fetoprotein level as objective response criteria, the overall response rate was 52% (13 out of 25 patients with evaluable disease). Ten out of 15 patients who had raised alpha-fetoprotein levels had more than 50% reduction and 8 patients had more than 90% reduction in alpha-fetoprotein level. Since analysis, 19 patients have died and 7 remain alive, giving a minimum median survival of 6 mo (range 1.2-16.6 mo), with 4 surviving more than 1 yr calculated from the day of treatment. There was only one patient who had late deterioration of liver function compatible with radiation hepatitis. There was no bone marrow toxicity documented in any patients. CONCLUSION: Treatment with intra-arterial 131I-L was well tolerated in patients with inoperable hepatocellular carcinoma and produced an objective response of 52% with median survival of 6 mo. A fractionated dose of 131I-L was feasible and the radiation dose could be escalated safely.

Carcinoma, Hepatocellular↗
PubMed1994

Calcium imaging of rhythmic network activity in the developing spinal cord of the chick embryo.

Video-rate imaging of spinal neurons loaded with calcium-sensitive dyes was used to investigate the calcium dynamics and cellular organization of spontaneously active rhythm-generating networks in the spinal cord of E9-E12 chick embryos. Spinal neurons were loaded with bath-applied fura-2am. Motoneurons were also loaded by retrograde labeling with dextran-conjugated, calcium-sensitive dyes. Dye-filled motoneurons exhibited large fluorescent changes during antidromic stimulation of motor nerves, and an increase in the 340/380 fura fluorescence ratio that is indicative of increased intracellular free calcium. Rhythmic fluorescence changes in phase with motoneuron electrical activity were recorded from motoneurons and interneurons during episodes of evoked or spontaneous rhythmic motor activity. Fluorescent responses were present in the cytosol and in the perinuclear region, during antidromic stimulation and network-driven rhythmic activity. Optically active cells were mapped during rhythmic activity, revealing a widespread distribution in the transverse and horizontal planes of the spinal cord with the highest proportion in the ventrolateral part of the cord. Fluorescent signals were synchronized in different regions of the cord and were similar in time course in the lateral motor column and in the intermediate region. In the dorsal region the rhythm was less pronounced and the signal decayed after a large initial transient. Video-rate fluorescent measurements from individual cells confirmed that fluorescent signals were synchronized in interneurons and in motoneurons although the time course of the signal could vary between cells. Some of the interneurons exhibited tonic elevations of fluorescence for the duration of the episode whereas others were rhythmically active in phase with motoneurons. At the onset of each cycle of rhythmic activity the earliest fluorescent change occurred ventrolaterally, in and around the lateral motor column, from which it spread to the rest of the cord. The results suggest that neurons in the ventrolateral part of the spinal cord are important for rhythmogenesis and that axons traveling in the ventrolateral white matter may be involved in the rhythmic excitation of motoneurons and interneurons. The widespread synchrony of the rhythmic calcium transients may reflect the existence of extensive excitatory interconnections between spinal neurons. The network-driven calcium elevations in the cytosol and the perinuclear region may be important in mediating activity-dependent effects on the development of spinal neurons and networks.

Animals↗
PubMed1993

Mucin synthesis and secretion in various human epithelial cancer cell lines that express the MUC-1 mucin gene.

Previous studies have suggested that mucin gene expression is tissue-specific; however, the relationship between unique mucin gene products and the biochemical properties of mucins is unknown. The purpose of this study was to determine the biochemical and molecular characteristics of mucin synthesized by adenocarcinoma cell lines derived from breast (ZR-75-1), stomach (MGC-803), pancreas (Capan-2), and lung (Chago K-1). Mucin was quantitated by [3H]glucosamine labeling and Sepharose CL-4B chromatography. The mucinous nature of the labeled high molecular weight glycoproteins (HMG) was verified by alkaline borohydride treatment, cesium chloride density gradient ultracentrifugation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Specific mucin gene expression was determined using cDNA probes for 2 distinct intestinal mucins (MUC-2 and MUC-3) and one breast cancer mucin (MUC-1). Specific core mucin proteins were confirmed by immunoblots using antibodies that recognize MUC-1, MUC-2, and MUC-3 core peptides. These experiments demonstrate that all cell lines contained HMG in the medium, cytosol, and membrane fractions. The HMG was mucinous in breast, pancreatic, and lung cell lines. In contrast, most of the HMG secreted by the gastric cell line was proteoglycan-like, due to its susceptibility to hyaluronidase, heparinase, and chondroitinase avidin-biotin complex. Ion-exchange (DEAE-Sephacel) chromatography of [3H]glucosamine-labeled HMG demonstrated that the acidic or basic nature of the mucin was different in all cancer cell lines tested. Despite these differences, mRNA and immunoblot analysis suggest that all cell lines predominantly express MUC-1 apomucin, small amounts of MUC-2 apomucin, and no MUC-3. Immunoprecipitation of MUC-1-type mucin using the 139H2 monoclonal antibody demonstrated that different sizes of mucin peptides were present in all cell lines, corresponding to the known length polymorphism of this mucin. The amount and nature of carbohydrate epitopes were analyzed by immunoblots using anti-T (peanut lectin), anti-Tn (91S8 monoclonal antibody), and anti-sialosyl Tn (JT10e monoclonal antibody). T and Tn antigens were significantly higher in breast and pancreatic cells as compared with lung and gastric cell lines. These findings correlated with increased activities of polypeptidyl N-acetylgalactosaminyl transferase and beta-1,3-galactosyltransferase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1993

Real-time imaging of neurons retrogradely and anterogradely labelled with calcium-sensitive dyes.

Membrane-impermeant calcium indicator dyes were used to retrogradely label dorsal root ganglia, spinal motoneurons and interneurons in the spinal cord of the chick embryo. The dyes were also used to label anterogradely primary afferent axons in the spinal cord and synaptic endings in the ciliary ganglion. Labelled neurons were imaged using digital videomicroscopy. Motoneurons and dorsal root ganglion cells exhibited a frequency-dependent change in fluorescence during antidromic stimulation. Single antidromic stimuli resulted in fluorescence transients that could be resolved in individual cells in real time. In addition, fluorescence changes could be recorded in motoneurons during episodes of bursting generated by rhythmic synaptic inputs from premotor networks. Stimulus-induced fluorescence signals were also detected in axons and synaptic endings labelled anterogradely. Optical signals were largely abolished in the absence of extracellular calcium. The results show that calcium changes can now be measured in identified populations of neurons and presynaptic terminals. The strong dependence of these signals on impulse activity suggests that the technique will be useful for monitoring the activity of identified neuronal populations. The calcium-dependent fluorescence signal probably results from cytosolic dye derived from diffusion which may limit the technique to situations in which the dye can be applied close (< 1 cm) to cell bodies.

Animals↗
PubMed1993

Evaluation of the Chinese version of the Hospital Anxiety and Depression Scale. A cross-cultural perspective.

The authenticity of the Chinese translation of the Hospital Anxiety and Depression Scale (HAD) was tested in a sample of medical students. The Chinese version demonstrated good agreement with the English original. There was a large difference between the mean anxiety and depression subscores. Factor analysis consistently yielded three factors, suggesting the existence of a somatic factor. It is suggested that a common cut-off point for the subscales of the HAD scale is not advisable and a multidimensional model for mood disorders is more appropriate in a cross-cultural context.

Adult↗