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Biomedical subjects

S Hung

Publications and source records attributed to S Hung.

At least 19 recordsLinked to original sources
PubMed2006

Vascular matrix adhesion and the blood-brain barrier.

The integrity of the cerebral microvasculature depends on the interaction between its component cells and the extracellular matrix, as well as reorganized cell-cell interactions. In the central nervous system, matrix adhesion receptors are expressed in the microvasculature and by neurons and their supporting glial cells. Cells within cerebral microvessels express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Endothelial cells and astrocytes within cerebral capillaries co-operate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells and oligodendroglia. Significant alterations in both cellular adhesion receptors and their matrix ligands occur during focal cerebral ischaemia, which support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood-brain permeability barrier and that modulation of these receptors contributes to alterations in the barrier during brain injury.

Animals↗
PubMed2004

Antiphospholipid antibodies bind to activated but not resting endothelial cells: is an independent triggering event required to induce antiphospholipid antibody-mediated disease?

INTRODUCTION: Antiphospholipid antibodies (aPL) cause thrombotic disease and recurrent pregnancy loss. Despite their name it is now clear that the antigen for most antiphospholipid antibodies is the phospholipid-binding protein beta(2) glycoprotein I (beta(2)GPI). However, beta(2) glycoprotein I is only antigenic for antiphospholipid antibodies when the protein is immobilised on a suitable surface such as phosphatidyl serine. It has been suggested that antiphospholipid antibodies bind to beta(2) glycoprotein I on the surface of resting endothelial cells and this in turn leads to endothelial activation and the initiation of thrombosis. However, as phosphatidyl serine is absent from resting endothelial cell membranes, we questioned this hypothesis. MATERIALS AND METHODS: The ability of human antiphospholipid antibody-containing sera and monoclonal antiphospholipid antibodies to interact with endothelial cells was examined using cell-based ELISAs employing human umbilical vein endothelial cells (HUVECs) as the antigen. The expression of adhesion molecules in response to treatment with antiphospholipid antibodies was also measured by a cell-based ELISA. Activation of NF kappa beta was examined using electrophoretic mobility shift assays (EMSAs). RESULTS: Neither monoclonal antiphospholipid antibodies nor human sera containing antiphospholipid antibodies bound to resting endothelial cells. In contrast, one monoclonal antiphospholipid antibody did bind to both activated and apoptotic endothelial cells. CONCLUSIONS: Antiphospholipid antibodies do not bind to resting endothelial cells nor do antiphospholipid antibodies activate resting endothelial cells. Rather, an independent triggering event is required to activate endothelial cells and subsequently some antiphospholipid antibodies may then bind to the activated endothelial cells and initiate a thrombogenic process.

Antibodies, Antiphospholipid↗
PubMed2001

Prospective study of zinc intake and the risk of age-related macular degeneration.

PURPOSE: Zinc is found in high concentrations in the retina and is hypothesized to reduce the risk of age-related macular degeneration (AMD). Any long-term benefit associated with dietary zinc intake has not been evaluated. METHODS: We followed 66,572 women and 37,636 men who were > or = 50 years old and had no diagnosis of AMD or cancer. Zinc intake from food, multivitamins, and supplements was assessed with a semiquantitative food-frequency questionnaire at baseline (in 1984 for women and in 1986 for men) and repeated during follow-up (twice for women, once for men). RESULTS: During 10 years of follow-up for women and 8 years of follow-up for men, we confirmed 384 incident cases of AMD (195 cases of the early form and 189 cases of the late form) associated with a visual acuity loss of 20/30 or worse. After multivariate adjustment for potential risk factors, the pooled relative risk was 1.13 (95% confidence interval [CI], 0.82 to 1.57; p-value, test for trend, 0.74) among participants in the highest quintile of total zinc intake (energy-adjusted median; 25.5 mg/day for women and 40.1 mg/day for men) compared with those in the lowest quintile (energy-adjusted median; 8.5 mg/day for women and 9.9 mg/day for men). The relative risk for highest compared with lowest quintile was 1.04 (95% CI, 0.59 to 1.83; p-value, test for trend, 0.54) for zinc intake from food. Subjects who took zinc supplements had a pooled multivariate relative risk of 1.04 (95% CI, 0.75 to 1.45). CONCLUSIONS: In these two large prospective studies, moderate zinc intake, either in food or in supplements, was not associated with a reduced risk of AMD.

Aged↗
PubMed2001

Prospective study of dietary fat and the risk of age-related macular degeneration.

BACKGROUND: The relation between intakes of total fat and specific types of fat and age-related macular degeneration (AMD) remains unclear. OBJECTIVE: Our objective was to examine prospectively the association between fat intake and AMD. DESIGN: We conducted a prospective follow-up study of participants in the Nurses' Health Study and the Health Professionals Follow-up Study. At baseline (1984 for women and 1986 for men), the study included 42743 women and 29746 men aged > or = 50 y with no diagnosis of AMD who were followed until 1996. Fat intake was assessed with a food-frequency questionnaire. RESULTS: We accrued 567 patients with AMD with a visual loss of 20/30 or worse. The pooled multivariate relative risk (RR) for the highest compared with the lowest quintile of total fat intake was 1.54 (95% CI: 1.17, 2.01; P for trend = 0.008). Linolenic acid was positively associated with risk of AMD (top versus bottom quintile of RR: 1.49; 95% CI: 1.15, 1.94; P for trend = 0.0009). Docosahexaenoic acid had a modest inverse relation with AMD (top versus bottom quintile of RR: 0.70; 95% CI: 0.52, 0.93; P for trend = 0.05), and >4 servings of fish/wk was associated with a 35% lower risk of AMD compared with < or = 3 servings/mo (RR: 0.65; 95% CI: 0.46, 0.91; P for trend = 0.009). CONCLUSIONS: Total fat intake was positively associated with risk of AMD, which may have been due to intakes of individual fatty acids, such as linolenic acid, rather than to total fat intakes per se. A high intake of fish may reduce the risk of AMD.

Age Factors↗
PubMed2000

Case of the month

Each month, we will present a challenging Case of the Month for The Green Journal readers, who must use their clinical acumen to arrive at the correct answer. We will also post the case each month on the Journal's web site (http://www.elsevier.com/locate/ajmselect). Several possible answers may be consistent with the case presentation; use your best judgment. Please send your answer (one per respondent) and indicate the case to which you are responding to The Green Journal at editors@amjmed.org or via FAX to (415) 447-2799. Only those answers with a complete mailing address will be considered. The correct answer will appear in the July issue of the Journal. The first five persons who submit correct answers will receive a free one-year subscription to the Journal. Colleagues of Drs. Tarng and Hung at the National Yang-Ming University School of Medicine in Taiwan are not eligible for this month's case. If you would like to contribute a case, please submit a brief synopsis (<250 words) to the editorial office. An individual may win only once per calendar year.

Journal Article↗
PubMed2000

The two sides of enzyme-substrate specificity: lessons from the aspartic proteinases.

Like most proteolytic enzymes, the aspartic proteinases bind substrates and most inhibitors within an extended active site cleft. Bound ligands typically adopt a beta-strand conformation. Interactions with groups on both sides of the cleft determine the primary as well as secondary specificity of the enzymes. We have pursued the discovery of the sometimes subtle distinctions between members of the aspartic proteinase family by two routes. In the first case, we have constructed sets of oligopeptide substrates with systematic variation in each position to assess interactions at one position at a time. In the second type of experiment, we have altered residues of the enzymes in order to test theories of selectivity. The combination of the two approaches has provided a better understanding of the forces involved in determining specificity of enzyme action.

Amino Acid Sequence↗
PubMed1999

The remarkably high excitation planetary nebula GC 6537.

NGC 6537 is an unusually high excitation point symmetric planetary nebula with a rich spectrum. Its kinematical structures are of special interest. We are here primarily concerned with the high resolution spectrum as revealed by the Hamilton echelle Spectrograph at Lick Observatory (resolution approximately 0.2 A) and supplemented by UV and near-UV data. These extensive data permit a determination of interstellar extinction, plasma diagnostics, and ionic concentrations. The photoionization models that have been used successfully for many planetary nebulae are not entirely satisfactory here. The plasma electron temperature of a photoionization model cannot much exceed 20,000 K, but plasma diagnostics show that regions emitting radiation of highly ionized atoms such as [NeIV] and [NeV] are much hotter, showing that shock excitation must be important, as suggested by the remarkable kinematics of this object. Hence, instead of employing a strict photoionization model, we are guided by the nebular diagnostics, which reveal how electron temperature varies with ionization potential and accommodates density effects. The predictions of the photoionization model may be useful in estimating ionization correction factor. In effect, we have estimated the chemical composition by using both photoionization and shock considerations.

Journal Article↗
PubMed1997

Neonatal outcome of very premature infants from multiple and singleton gestations.

OBJECTIVES: Our purpose was to determine whether, in the era of surfactant treatment, very premature neonates from multiple gestations have outcomes similar to those of singletons. STUDY DESIGN: We collected data on 572 infants (369 singletons, 203 multiple gestation) born and cared for at a single institution from July 1, 1992, through Dec, 31, 1994, of gestational ages 24 to 32 weeks. We compared singleton infants with infants from multiple gestations within gestational age categories 24 to 26 weeks, 27 to 29 weeks, and 30 to 32 weeks. RESULTS: Infants of multiple gestations were more likely to have been born by cesarean section. The incidences of respiratory distress syndrome and bronchopulmonary dysplasia were similar, except that respiratory distress syndrome was more frequent in infants of multiple gestations at 30 to 32 weeks. Infants of multiple gestations from 27 to 29 weeks were more likely to have at least one of the following complications: patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, or retinopathy of prematurity. Further analysis suggested that this increase is unlikely to cause a difference in long-term outcome. The survival to discharge increased from 79% (multiples) and 81% (singletons) at 24 to 26 weeks to 98% (multiples) and 96% (singletons) at 30 to 32 weeks. CONCLUSIONS: Incidences of significant neonatal problems in very premature infants from multiple gestations who are born alive are little different from those of singletons. These data should have an impact on decision making in the perinatal and neonatal care of infants of multiple gestations.

Birth Weight↗
PubMed1994

Inhibition of calcineurin by a novel FK-506-binding protein.

FK-506, a potent immunosuppressive drug, acts during the commitment phase of T-lymphocyte activation to block a subset of calcium-associated events necessary for transcription of certain early lymphokine genes. The drug binds to an abundant, cytosolic 11.8-kDa protein termed the FK-506-binding protein (FKBP12). The FKBP12.FK-506 complex inhibits calcineurin, a calcium-dependent phosphatase that is a component of the signal transduction pathway leading to early lymphokine gene transcription. FKBP12 is one member of a growing gene family. Prior to this report, all other FKBP family members had been irrelevant to the mechanism of action of FK-506 because no other FKBP.FK-506 complexes were able to bind and inhibit calcineurin. Here, we report the purification and characterization of a novel FK-506-binding protein, FKBP12.6. Having 85% amino acid sequence identity to FKBP12, FKBP12.6 is, among the FKBPs, most closely related to FKBP12. When complexed with FK-506, FKBP12.6 binds to and inhibits calcineurin, making it only the second FKBP discovered thus far to do so. The ability to inhibit calcineurin establishes the potential relevance of FKBP12.6 to the immunosuppressive or toxic side effects of FK-506.

Amino Acid Isomerases↗
PubMed1994

A phase II trial of recombinant leukocyte interferon plus doxorubicin in patients with hepatocellular carcinoma.

A Phase II trial of combination therapy with recombinant leukocyte interferon (alpha IFN) and doxorubicin was performed in patients with unresectable hepatocellular carcinoma. alpha IFN was administered at a starting dose of 20 x 10(6) U/m2 intramuscularly or subcutaneously with doxorubicin 20 mg/m2 intravenously weekly x 3 weeks followed by a 2-week period rest. There were 22 patients entered into the study. Among the 21 patients, there were 2 partial responses (10%), one minor response, and one patient had stable disease. Toxicity was generally tolerable, with fever, fatigue, and myelosuppression being the most common side effects. This combination of weekly recombinant leukocytic interferon and doxorubicin has modest and limited activity in hepatocellular carcinoma.

Adult↗
PubMed1993

The mechanism of action of FK-506 and cyclosporin A.

FK-506 and cyclosporin A (CsA) are potent immunosuppressive agents used clinically to prevent tissue rejection. Interest in the development of more effective immunosuppressive drugs has led to an intense effort toward understanding their biochemical mechanism of action with the result that these compounds have now become powerful tools used in deciphering the signal transduction events in T lymphocyte activation. Although chemically unrelated, FK-506 and CsA exert nearly identical biological effects in cells by inhibiting the same subset of early calcium-associated events involved in lymphokine expression, apoptosis, and degranulation. FK-506 binds to a family of intracellular receptors termed the FK-506 binding proteins (FKBPs). CsA binds to another family of intracellular receptors, the cyclophilins (Cyps), distinct from the FKBPs. The similarities between the mechanisms of action of CsA and FK-506 converge upon the calcium- and calmodulin-dependent serine-threonine protein phosphatase calcineurin (CaN). Both the FKBP/FK-506 complex and the Cyp/CsA complex can bind to calcineurin, thereby inhibiting its phosphatase activity. Calcineurin, a component of the signal transduction pathway resulting in IL-2 expression, catalyzes critical dephosphorylation events required for early lymphokine gene transcription.

Amino Acid Isomerases↗
PubMed1992

Characterization of high molecular weight FK-506 binding activities reveals a novel FK-506-binding protein as well as a protein complex.

The immunoregulant FK-506 potently inhibits particular calcium-associated signal transduction events that occur early during T-lymphocyte activation and during IgE receptor-mediated exocytosis in mast cells. FK-506 binds to a growing family of receptors termed FK-506-binding proteins (FKBPs), the most abundant being a 12-kDa cytosolic receptor, FKBP12. To date, there is no formal evidence proving that FKBP12 is the sole receptor mediating the immunosuppressive effects or toxic side effects of FK-506. Using gel filtration chromatography as an assay for novel FK-506-binding proteins, we identified FK-506 binding activities in extracts prepared from calf brain and from JURKAT cells. Both of these new activities comigrated with apparent molecular masses of 110 kDa. However, further characterization of both binding activities revealed that the two are not identical. The 110-kDa activity observed in brain extracts appears to be the FKBP12.FK-506.calcineurin (CaN) complex previously reported (Liu, J., Farmer, J., Lane, W., Friedman, J., Weissman, I., and Schreiber, S. (1991) Cell 66, 807-815) while the 110 kDa activity observed in JURKAT cells is a novel FK-506-binding protein. Our characterization of the FKBP12.FK-506.CaN complex reveals a dependence upon calmodulin (CaM) for formation of the complex and demonstrates that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase activity. The novel FK-506-binding protein in JURKAT cells has been purified to homogeneity, migrates with an apparent mass of 51 kDa on denaturing gels, and has been termed FKBP51. Like FKBP12, FKBP51 has PPIase activity, but, unlike FKBP12.FK-506, FKBP51.FK-506 does not complex with or inhibit the phosphatase activity of, CaN. These results indicate that complex formation with CaN may not be a general property of the FKBPs. Peptide sequencing reveals that FKBP51 may be similar, if not identical, to hsp56, a component of non-transformed steroid receptors.

Amino Acid Isomerases↗
PubMed1991

Information-seeking triggered by age.

Age labels may lead to the seeking of age-stereotypic information from target individuals. Using Carver and de la Garza's information-seeking procedure (which asked respondents to judge the relative importance of various kinds of information they would glean from drivers involved in an automobile accident for assigning accident responsibility), but extending it to a wider life span (16 to 91 years of age) and to both genders, we generalized earlier findings to a similar undergraduate sample (n = 437) in another country. Also demonstrated for the first time is the fact that ageist information-seeking across the life span was independent of the driver's gender, the participant's age, and the participant's gender. Specifically, participants wanted to know from younger drivers about their driving conduct (whether they had been drunk and speeding), and from older drivers about their capacity for driving (mental competence, vision, and health). The seeking of environmental information (car safety and road conditions) did not vary with the age of driver in any systematic way.

Accidents, Traffic↗
PubMed1978

Familial Cushing's syndrome.

Cushing's syndrome has been demonstrated in four of seven siblings with clinical manifestations appearing around puberty in three of the four siblings. The only other associated findings in these cases were short stature and disturbed carbohydrate metabolism. Adenomatous hyperplasia of the adrenal glands was demonstrated in 3 of the patients, and a virilizing adrenal carcinoma in the fourth sibling. The pathogenesis of the adrenocortical disorders in these siblings is discussed.

Adolescent↗