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Biomedical subjects

S Chung

Publications and source records attributed to S Chung.

At least 181 records · Page 10Linked to original sources

A family of calcium-dependent potassium channels from rat brain.

By incorporating rat brain plasma membrane vesicles into planar lipid bilayers, we have found and characterized four types of Ca2(+)-activated K+ channels. The unitary conductances of these channels are 242 +/- 14 pS, 236 +/- 16 pS, 135 +/- 10 pS, and 76 +/- 6 pS in symmetrical 150 mM KCI buffers. These channels share a number of properties. They are all activated by depolarizing voltages, activated by micromolar concentrations of internal Ca2+ with a Hill coefficient for Ca2+ activation of between 2 and 3, noninactivating under our assay conditions, blocked by low millimolar concentrations of TEA from the outside, apamin-insensitive, and very selective for K+ over Na+ and Cl-. Three of the four channels are also blocked by nanomolar concentrations of charybdotoxin. One of the high conductance Ca2(+)-activated K+ channels is novel in that it is not blocked by charybdotoxin and exhibits gating kinetics highlighted by long closed times and long open times. This family of closely related Ca2(+)-activated K+ channels may share structural domains underlying particular functions.

Animals↗

Reverse-flow postauricular arterial flap for auricular reconstruction.

Two patients with an ear defect, each reconstructed with a reverse-flow postauricular arterial flap are presented; one defect was caused by accidental exposure of bare cartilage at the posterior helix and the other by traumatic loss of earlobe. After the flaps were transposed, a line of auditory signals was dictated by Doppler probing, which suggested the presence of reverse blood flow in the flaps from the anteroauricular vessels. We believe that the reverse-flow postauricular arterial flap is a reliable and convenient optional tool in the reconstruction of auricular defects.

Adult↗

Importance of introns for expression of mouse ribosomal protein gene rpL32.

The importance of intronic sequences for expression of the mouse ribosomal protein gene rpL32 was evaluated by transfection experiments with a series of mutant constructs in which one or more of the three rpL32 introns was totally or partially deleted. When transiently transfected into monkey kidney (COS) cells or stably transfected into mouse L cells, a mutant that lacked all three introns was completely inactive. Constructs that contained intron 1, either alone or in combination with another intron, were expressed as efficiently as was the normal intact rpL32 gene. Constructs that lacked intron 1 but contained another spliceable intron, even one from a foreign gene, were expressed at about 10 to 20% of the maximum level. These results indicated that intron 1 contains an element that increases the level of expression by 5- to 10-fold. A comparison of internal deletion mutants localized the element to within the first 27 base pairs of intron 1. Nuclear run-on experiments with stably transfected COS cells demonstrated that this element functions at the transcriptional level. The element was inactive when translocated to a position upstream of the transcriptional start site or to a position within intron 3, which indicated that it does not have the properties of a typical enhancer. From these and other results, we conclude that introns have both a general and a specific role in rpL32 expression. The general role, which can be satisfied by any spliceable intron, is to ensure an efficient yield of RNA transcripts. The specific role is uniquely attributable to intron 1, which contains a transcriptional regulatory element near its 5' end.

Animals↗

Gastric outlet obstruction masquerading as anorexia nervosa.

A 30-year-old Chinese housewife presenting with what appeared to be late-onset anorexia nervosa was subsequently found to have peptic ulcer disease complicated by gastric outlet obstruction. Surgical treatment led to rapid improvement of body weight but not immature personality. Extra caution should be exercised in the diagnosis of anorexia nervosa presenting with atypical features in a community in which that condition is rare.

Adult↗

A morphometric study of muscle mitochondria in cytochrome c oxidase deficiency.

Quantitative analysis of mitochondrial size and its percentage of total fibre volume in different muscle fibre types was performed on biceps brachii muscles of controls aged from 9 months to 10 years, and patients aged from 8 months to 14 years, with cytochrome c oxidase (CCO) deficiency confirmed by both histochemical and biochemical analyses. The disease was classified into 2 subgroups: one not containing ragged-red fibres (RRF) (group I), and one containing RRF (group II). Relationship between type 1 and 2 fibres in mitochondrial size and percentages of total fibre volume showed significant differences in the controls and group I. A comparison of the controls and group I did not show significant differences in mitochondrial size, but abnormally enlarged mitochondria were occasionally observed in the latter. In group I, statistical differences were observed in mitochondrial percentage of total fibre volume, though these differences remained in the control range, suggesting the presence of mild morphological changes in mitochondria on electron microscopy. In group II, mitochondrial size and its percentage of total fibre volume were markedly increased in both type 1 and 2 fibres, with no statistical differences observed between the 2 fibre types.

Child↗

Natural cell-mediated cytotoxicity to cells infected with infectious bovine rhinotracheitis virus.

Cell-mediated cytotoxicity against viral-infected cells was demonstrated in a 6-hr 51Cr release assay. Peripheral blood mononuclear leukocytes from both infectious bovine rhinotracheitis virus (IBRV)-infected and noninfected cattle exhibited preferential lysis against IBRV-infected primary bovine embryonic kidney (BEK) cells compared to cells infected with pseudorabies virus and noninfected BEK cells. Addition of specific antibody to the assay did not enhance cytotoxicity. The effector cell was a nonadherent cell which was either spontaneously enriched or generated during in vitro cultivation. Maximal cytotoxic activity was detected in peripheral blood mononuclear cells cultured for 3 to 5 days. Several factors affected the magnitude of cytotoxicity during the assay: target cell type, concentration of viral inoculum, duration of effector and target cell contact. It is suggested that target cell lysis was a form of natural cell-mediated cytotoxicity mediated by a cell which has different characteristics from the typical human and murine NK cell.

Animals↗

Influence of long-term aldose reductase inhibitor therapy on autonomic dysfunction of urinary bladder, stomach and cardiovascular systems in diabetic patients.

The effects of the aldose reductase inhibitor (ARI) sorbinil (250 mg/day) were tested in an open-label pilot study over 1 year, in eight diabetics with peripheral neuropathy, seven of whom had symptomic autonomic neuropathy (AN). Autonomic function studies of the urinary bladder, stomach and cardiovascular system were performed at baseline, 6 and 12 months. Six patients reported improvement in symptoms of AN by 6 months which was maintained or further improved by 12 months. Bladder sensation, as measured by cystometrographic parameters, improved at 6 months (P less than 0.02- less than 0.04), but by 12 months had reverted to baseline. Residual urine volume decreased at 6 months (P less than 0.06) and 12 months (P less than 0.06). Vagally mediated gastric acid secretion improved at 6 months (P less than 0.06); the subgroup of patients with subnormal secretion showed improvement to the normal range at 6 months (P less than 0.03). Gastric emptying of solid food was normal in six of eight subjects and showed no significant change at 6 months. Both patients with delayed emptying normalized. No change in beat-to-beat variability in heart rate with respiration was noted. Resting minimum heart rate decreased at 12 months (P less than 0.05). Glycohemoglobin levels showed no statistically significant changes. No toxic reactions were observed. These data suggest a beneficial effect of ARI treatment on symptomatic and asymptomatic manifestations of diabetic autonomic neuropathy and indicate a need for large controlled trials.

Adult↗

Developmental regulation of DNase I-hypersensitive sites in Dictyostelium discoideum.

We have studied two regions of Dictyostelium discoideum chromatin and identified several DNase I-hypersensitive sites in these regions. One of these sites is located about 300 to 500 bases upstream of the transcriptional start site of a gene that is expressed at all stages of development. This site is present in both vegetative cells and postaggregation cells. Another hypersensitive site is associated with a gene that is expressed only after the multicellular stage. This site is located about 400 bases upstream of the start site, and it is present only in postaggregation cells. Thus, much like higher eucaryotes, D. discoideum contains DNase I-hypersensitive sites that may be involved in the regulation of the genes with which they are associated.

Cell Differentiation↗

Directional control of site-specific recombination by bacteriophage lambda. Evidence that a binding site for Int protein far from the crossover point is required for integrative but not excisive recombination.

Phage lambda controls its integration and excision by differential catalysis of the forward and reverse reactions. The lambda Int protein is required for both directions, but Xis for excision only. To investigate the substrate requirements for directional control, we have characterized two mutations of the phage attachment site that are defective in integrative but not excisive recombination. Both of these mutations produce the same base change in the P'3 binding site for Int protein 79 base-pairs from the center of the crossover region for site-specific recombination. We infer that differential utilization of this distant binding site is crucial for directional control of recombination.

Bacteriophage lambda↗

Monoclonal antibodies to cystic fibrosis antigen.

A series of monoclonal antibodies has been prepared against a granulocyte antigen previously shown to be present in the serum of individuals homozygous or heterozygous for the cystic fibrosis (CF) gene. The specificity of the monoclonals was established by their ability to remove the antigen (CF antigen) from serum. The monoclonals defined at least two epitope regions on CF antigen, thus permitting the establishment of a two-site sandwich enzyme-linked immunosorbent assay (ELISA). Using the ELISA significant differences in levels of CF antigen were demonstrated in serum samples from CF homozygotes, CF heterozygotes and normal controls.

Antibodies, Monoclonal↗

Common acylcarboxypeptidase A intermediates for ester substrates containing different cleaving alcohols.

In the carboxypeptidase A-catalyzed ester hydrolysis of the trans-alpha-(benzoylamino)cinnamoyl derivatives of both L-mandelate and L-beta-phenyllactate, kcat stands for the breakdown of an additional enzyme-substrate complex (ES'). The pH dependence of kcat indicates that ES' is the anhydride acylcarboxypeptidase A formed by the nucleophilic attack of Glu-270 for both of the ester substrates. Furthermore, the very similar kcat values for the two ester substrates which share a common acyl moiety strongly suggest that common acylenzyme intermediates are involved, whose breakdown process is little affected by the cleaved alcohol portions. This provides the most direct evidence that has been reported for the nucleophilic mechanism of the carboxypeptidase A action.

Alcohols↗

A monoclonal antibody-based immunoassay for human lactoferrin.

Monoclonal antibodies against human lactoferrin define at least 3 and possibly as many as 6 different epitopes. A sandwich enzyme-linked immunoassay, using monoclonals against different epitopes, has been optimised for the measurement of serum lactoferrin. In 35 samples from healthy adults the mean lactoferrin content of serum from blood clotted overnight was 0.54 +/- 0.26 micrograms/ml.

Adult↗