Biomedical subjects

S Y Cheng

Publications and source records attributed to S Y Cheng.

At least 73 records · Page 4Linked to original sources

PubMed1994

Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro).

We report a family with familial amyloid polyneuropathy (FAP), showing an early-onset and a fatal outcome before age 30. Transthyretin (TTR) gene analysis showed one point mutation (T-->C change) in the second base of codon 55, and the corresponding amino acid substitution of proline (Pro) for leucine (Leu) was confirmed at the protein level. This is the first FAP family of Taiwanese origin demonstrating a causative gene abnormality, and FAP with TTR-Pro55 was considered to be more serious compared with other forms of FAP.

Adolescent↗

PubMed1994

[Ureaplasma urealyticum infection in spontaneous abortion].

Ureaplasma urealyticum in aborted tissue and cervical mucus were examined in 40 women with spontaneous abortion (test group), 20 women of induced abortion and 20 healthy pregnant women (control group). The results showed that the positive isolation rate of ureaplasma urealyticum was significantly higher in the test group than that in the control group (55.0% vs 10.0%). The detection rate of ureaplasma urealyticum increased along with the number of spontaneous abortion. It indicated that ureaplasma urealyticum might be a cause of unexplained spontaneous abortion.

Abortion, Spontaneous↗

PubMed1994

[A study on the pectinase-producing abilities of Aspergillus flavus in grain of Zhejiang Province].

Eighty strains of Aspergillus flavus were isolated from 110 specimens of rice, wheat flour and malt, and their pectinase-producing abilities were studied in toxigenic and non-toxigenic strains. Levels of pectinase-production by A. flavus were determined with measuring the diameter of the colourless and transparent zone formed around the colonies stained with ruthenium red. Toxigenic strains with high levels of pectinase-production (with a diameter of transparent zone more than 5 mm) accounted for 82.6% and non-toxigenic strains for 42.1% of the total, respectively, and their difference reached a significant level. The level of pectinase-production in toxigenic strains was higher than that in non-toxigenic ones.

Aspergillus flavus↗

PubMed1993

Conformational changes of human beta 1 thyroid hormone receptor induced by binding of 3,3',5-triiodo-L-thyronine.

To understand the structural basis in the hormone-dependent transcriptional regulation of human beta 1 thyroid hormone receptor (h-TR beta 1), we studied the conformational changes of h-TR beta 1 induced by binding of 3,3',5-triiodo-L-thyronine (T3). h-TR beta 1 was treated with trypsin alone or in the presence of T3, thyroid hormone response element (TRE) or T3 together with TREs. Without T3, h-TR beta 1 was completely digested by trypsin. Binding of TREs had no effect on the tryptic digestion pattern. However, T3-bound h-TR beta 1 became resistant to tryptic digestion and yielded trypsin-resistant peptide fragments with molecular weight of 28,000 and 24,000. Chymotryptic digestion also yielded a T3-protected 24 Kd peptide fragment. Using anti-h-TR beta 1 antibodies and amino acid sequencing, the 28 Kd fragment was identified to be Ser202-Asp456. The 24 Kd tryptic fragments were found to be Lys239-Asp456 and Phe240-Asp456. The 24 Kd chymotryptic fragment was identified to be Lys235-Asp456. The structural changes as a result of T3 binding could serve as a transducing signal to modulate the gene regulating activity of h-TR beta 1.

Amino Acid Sequence↗

PubMed1993

Structure of the hormone binding domain of human beta 1 thyroid hormone nuclear receptor: is it an alpha/beta barrel?

To understand the structure of the hormone binding domain (HBD) of human beta 1 thyroid hormone nuclear receptor (h-TR beta 1), truncated h-TR beta 1 fragments, MD32 (M169-D456), KD29 (K201-D456), DD28 (D211-D456), KD25 (K235-D456), and KP28 (K201-P448), were analyzed by circular dichorism (CD). MD32 and KD29 show intense CD spectra with double minima at 222 and 208-210 nm, indicating the presence of extensive regions of alpha-helix. DD28 and KD25 have spectra which are reduced in intensity with minima around 215 nm, characteristic of a beta-sheet. The observed spectra are compatible with sequence analysis which predicts that HBD contains alternating stretches of alpha-helix and beta-strand. These extensive decreases in secondary structure in DD28 and KP28 in which the predicted first beta-strand or last alpha-helix was deleted, respectively, were accompanied by the loss of hormone binding activity. On the basis of these results, we suggest a new model for h-TR beta 1 consisting of the known DNA binding domain linked by an alpha-helical hinge to the HBD, with the tertiary structure of an alpha/beta barrel. The model is compatible with previous chemical and genetic studies on the structure of this protein.

Amino Acid Sequence↗

PubMed1993

Ophthalmologic manifestations in MELAS syndrome.

We describe a 15-year-old boy with full-blown mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO). He presented with visual disturbance, hearing impairment, continuous partial epilepsy on the right aspect of the face, and right hemiparesis since the age of 13. Four months later, he experienced another strokelike episode with continuous partial epilepsy on the left hand. Serial computed tomographic scans revealed bilateral parieto-occipital hypodense lesions with gyral enhancement and an additional low-density lesion in the right frontal area 4 months later, respectively. Results of laboratory examinations disclosed lactic acidosis and mitochondrial myopathy with many ragged-red fibers. To identify the defective gene in mitochondrial DNA, a simple molecular test was performed by using restriction endonuclease Apa I. A transition from A to G was found at nucleotide position 3243 of the tRNA(Leu) gene. Interestingly, the patient also had marked external ophthalmoplegia and ptosis commonly found in patients with CPEO. Therefore, we suggest that ophthalmoplegia also occurs in the MELAS syndrome.

Adolescent↗

PubMed1993

One-step immunoaffinity purification of human beta 1 thyroid hormone receptor with DNA and hormone binding activity.

An efficient and versatile method to purify large amounts of active human beta 1 thyroid hormone receptor (h-TR beta 1) was developed. Using a T7 expression system, h-TR beta 1 was overexpressed in Escherichia coli. Approx. 80% of the expressed receptor protein was concentrated in the insoluble inclusion bodies and approximately 20% was in the soluble form (h-TR beta 1-S). h-TR beta 1-S was conveniently purified by one immunoaffinity chromatographic step. From 1 l of cell culture, approx. 0.1 mg of purified h-TR beta 1-S was obtained. The purified h-TR beta 1-S binds to 3,3',5-triiodo-L-thyronine with a Ka = 2 x 10(9) M-1 and exhibits analog specificity. The purified h-TR beta 1-S also binds to T3 response elements (TRE) with different orientation in the half-sites with differential activity. In addition, binding of h-TR beta 1-S to TREs was enhanced by retinoid X receptor. These results indicate that the purified h-TR beta 1-S retains its hormone and DNA binding activity. The purified h-TR beta 1-S is suitable for structural and functional studies. This method could be used to purify h-TR beta 1 or rat TR beta 1 expressed in insect cells or yeast.

Base Sequence↗

PubMed1993

Region-specific anti-thyroid hormone receptor (TR) antibodies detect changes in TR structure due to ligand-binding and dimerization.

There are multiple factors that potentially can induce structural changes in DNA-bound thyroid hormone receptors (TRs) including protein-protein interactions, ligand-binding to TRs, and the thyroid hormone response element (TRE) sequence. We used a battery of anti-TR antibodies that recognize the amino-terminal, hinge, or carboxy-terminal regions of TRs to study changes in the epitope regions of in vitro translated TRs in electrophoretic mobility shift assays. We found that the carboxy-terminal and hinge region antibodies recognized TR homodimers but not TR/T3-receptor auxiliary protein or TR/retinoid X receptor heterodimers. The amino-terminal antibodies detected conformational changes due to ligand binding. In contrast, each antibody recognized TR complexes bound to TREs containing half-sites arranged in three different orientations. These results suggest that dimerization with nuclear proteins and ligand-binding, rather than the orientation of TRE half-sites, cause changes in several TR subregions.

Antibody Specificity↗

PubMed1993

Interaction of human beta 1 thyroid hormone receptor and its mutants with DNA and retinoid X receptor beta. T3 response element-dependent dominant negative potency.

Mutations in the human beta thyroid hormone receptor (h-TR beta) gene are associated with the syndrome of generalized resistance to thyroid hormone. We investigated the interaction of three h-TR beta 1 mutants representing different types of functional impairment (kindreds ED, OK, and PV) with different response elements for 3,3',5-triiodothyronine (T3) and with retinoid X receptor beta (RXR beta). The mutant receptors showed an increased tendency to form homodimers on a palindromic T3-response element (TREpal), a direct repeat (DR + 4), and an inverted palindrome (TRElap). On TRElap, wild type TR binding was decreased by T3, while the mutant receptors showed a variably decreased degree of dissociation from TRElap in response to T3. The extent of dissociation was proportional to their T3 binding affinities. RXR beta induced the formation of h-TR beta 1:RXR beta heterodimers equally well for mutants and the wild type h-TR beta 1 on these T3 response elements. However, the T3-dependent increase in heterodimerization with RXR beta was absent or reduced for the mutant TRs. Transient transfection studies indicated that the dominant negative potency was several-fold more pronounced on the TRElap as compared to TREpal or DR + 4. In CV-1 and HeLa cells, transfection of RXR beta could not reverse the dominant negative action. These results demonstrate that the binding of mutant h-TRs to DNA, as well as their dominant negative potency, are TRE dependent. In addition, competition for DNA binding, rather than for limiting amounts of RXR beta, is likely to mediate the dominant negative action.

Animals↗

PubMed1993

Electrodiagnostic studies in myasthenia gravis.

Forty-three patients with myasthenia gravis (MG) were studied to compare the sensitivity of repetitive nerve stimulation (RNS) test with single fiber electromyography (SFEMG) in the diagnosis of MG. SFEMG was abnormal in 81% (35 of 43 cases), while RNS test was abnormal in 53% (23 of 43 cases). In ocular MG, SFEMG showed a much higher positive rate (70%, 16 of 23 cases) than RNS test (22%, 5 of 23 cases). Both studies had similar abnormal rates in the generalized group. In patients studied with SFEMG in the EDC muscle, the clinical severity was closely correlated with jitter abnormality. We conclude that SFEMG is more sensitive than RNS test in the diagnosis of MG, especially in the ocular group.

Adolescent↗

PubMed1993

Type I familial amyloid polyneuropathy--report of a family in Taiwan.

We report three cases of histologically verified systemic amyloidosis with polyneuropathy. Common to them were early onset progressive peripheral sensorimotor disturbance starting in the legs and prominent autonomic dysfunctions such as postural hypotension, anhidrosis, and loss of pupillary light reflexes. Other characteristic features included vomiting, alternating diarrhea and constipation, opacities of the vitreous bodies, and congestive heart failure. All these clinical manifestations resemble type I familial amyloid polyneuropathy described by Andrade in 1952 from Portugal. Sural nerve biopsy stained with Congo red showed typical green birefringence under polarized light microscope. Histologically verified familial cases of this form of amyloid polyneuropathy have not been reported from Taiwan before.

Adolescent↗

PubMed1993

[The effect of intracranial pressure caused by airway suction in hypertensive intracerebral hemorrhagic comatose patients].

Ten hypertensive intracerebral hemorrhagic comatose patients in the Neurosurgical Intensive Care Unit were involved in this study. The ten were within the range of 5 to 8 by Glasgow Coma Scale, and all had undergone tracheostomy. During suction of the airway for 20 seconds in 4 areas (trachea, bronchus, nasal and oral cavities), the data of intracranial pressure (ICP), arterial blood pressure, pulse rate (PR) and respiration rate (RR) were recorded. Results were analyzed for ICP, mean arterial blood pressure (MABP), PR, RR, and cerebral perfusion pressure (CPP) at the 5th, 10th, 15th and 20th seconds in the above-mentioned areas. The ICP was found to be significantly increased, and above the 20 mmHg mark, during suction of the bronchus or nasal cavity for 5 seconds. The MABP also showed significant increase, to above the 110 mmHg mark during 5-second suction of the trachea or nasal cavity or during suction of the bronchus or oral cavity for 10 seconds. However, during the suction of the four airway areas, PR and RR were less influenced and the CPP was not decreased or significantly changed. The conclusion of this study was that suction in the areas of trachea, bronchus and nasal cavity, should not exceed 5 to 10 seconds; in the oral cavity, it may be done within 10 to 15 seconds and at each procedure of airway suction. If it is not possible to clean the sputum or secretion in one procedure, the patient should be allowed to rest for about one minute or become stabilized as determined by watching the monitors of ICP, BP, PR, and RR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Regulation by thyroid hormone of the synthesis of a cytosolic thyroid hormone binding protein during liver regeneration.

To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58-M2 was measured by metabolic labeling of primary cultures derived from the regenerating liver of euthyroid, hypo- or hyperthyroid rats. During regeneration, the increase in the liver/body weight ratio is approximately 25% higher in hyper- than in hypothyroid rats. However, T3 has no effect on the rate of overall liver regeneration observed in four days. In mature liver, T3 increased the synthesis of p58-M2 by approximately 2.5-fold. During regeneration, however, the change in the synthesis of p58-M2 varied with the thyroid status. In euthyroid rats, the synthesis of p58-M2 continued to increase up to 2-fold during liver regeneration. In hyperthyroid rats, after an initial increase by 1.5-fold on day 1, the synthesis of p58-M2 subsequently declined during regeneration. In hypothyroid rats, the synthesis of p58-M2 remained virtually unchanged during regeneration. These results indicate that T3 regulates the synthesis of p58-M2 in mature and regenerating liver.

Animals↗

PubMed1992

Regulation of thyroid hormone receptor-mediated transcription by a cytosol protein.

Thyroid hormone receptors (TRs) are members of the steroid hormone/retinoic acid receptor superfamily, which regulate homeostasis, development, and differentiation. Their transcriptional activity is modulated by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The present study evaluated the effect of the availability of cytoplasmic T3 on the modulation of transcriptional responses of the TRs. In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3. The in vivo monomer-tetramer interconversion is regulated by glucose via fructose 1,6-bisphosphate. At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein. By using a transient transfection system, a concomitant reduction in the transcriptional activity of the human beta 1 thyroid hormone receptor was detected in both cell lines. In the absence of glucose, the transcriptional activity of the human beta 1 thyroid hormone receptor in JEG-3 and COS-1 cells was reduced by 65-75% and 90-95%, respectively. However, glucose had no effect on the basal transcriptional activity. These findings demonstrate an important prenuclear step in the modulation of the gene regulating activity of the TRs.

Animals↗

PubMed1992

Phosphorylation stimulates the transcriptional activity of the human beta 1 thyroid hormone nuclear receptor.

The role of phosphorylation on the gene activation activity of the human beta 1 thyroid hormone nuclear receptor (h-TR beta 1) was examined. h-TR beta 1 was found to be a phosphoprotein when expressed in COS-1 cells, with serine, threonine, and tyrosine (85:10:5) as the phosphorylation sites. Okadaic acid (a potent inhibitor of phosphatases 1 and 2A) at 0.1, 0.25, and 0.5 microM increased the phosphorylation of h-TR beta 1 by 3-, 7-, and 11-fold, respectively. The increase in phosphorylation was accompanied by a concomitant increase in phosphorylation was accompanied by a concomitant increase in receptor-mediated transcription in transient transfection assays. h-TR beta 1 purified from Escherichia coli was phosphorylated in vitro by the endogenous kinase from cellular extracts. Serine, threonine, and tyrosine were phosphorylated in a similar ratio to that found in COS-1 cells. The in vitro phosphorylation was stimulated by okadaic acid. Phosphorylation did not affect the binding of h-TR beta 1 to 3,3',5-triiodo-L-thyronine. However, phosphorylation of h-TR beta 1 resulted in an increase of its binding to DNA and conferred on it the ability to bind to nuclear accessory proteins. The results indicate that phosphorylation plays an important role in the transcriptional activity of h-TR beta 1.

Adenosine Triphosphate↗

PubMed1992

Transcriptional stimulation by thyroid hormone of a cytosolic thyroid hormone binding protein which is homologous to a subunit of pyruvate kinase M1.

We have recently shown that the monomer of rat pituitary pyruvate kinase subtype M1 (p58-M1) is a cytosolic binding protein for 3,3',5-triiodo-L-thyronine (T3). To understand the role p58-M1 plays in thyroid hormone action, we examined the regulation of p58-M1 by T3 in GH3 cells. Expression of p58-M1 was evaluated by metabolically labeling GH3 cells cultured in regular medium, thyroid hormone depleted medium (Td medium), or Td medium supplemented with T3 (Td + T3 medium) followed by immunoprecipitation. T3 stimulates the expression of p58-M1 by 2-fold. Analysis by pulse-chase experiments indicates that the increased expression is not due to the increase of stability of p58-M1. Northern analysis of mRNA prepared from cells cultured in regular, Td, or Td + T3 medium demonstrates that T3 increases the accumulation of cytoplasmic mRNA by 2-fold. Nuclei from cells cultured in the three conditions were prepared, and the rates of synthesis of nascent nuclear RNA were compared by an in vitro transcription assay. Addition of T3 stimulates the rate of transcription by 2-fold. The parallel and identical magnitude in the increase of transcription rate and the accumulation of mRNA indicates that T3 stimulates the synthesis of p58-M1 by increasing the transcriptional activity of its gene.

Animals↗

PubMed1992

A sensitive and rapid in situ immunoassay to quantitatively determine the cellular antigens in intact cultured cells.

A sensitive and rapid in situ immunoassay to quantitatively determine the cellular antigens in intact cells was developed. Antigens located in plasma membrane, endosome, cytosol, lysosome or endoplasmic reticulum of cultured cells were fixed in situ and reacted with monoclonal antibodies after permeabilization of cells with saponin. The antigen-antibody complexes were quantified by colorimetric method of peroxidase-substrate reaction. Epidermal growth factor receptor, monomer of pyruvate kinase M2 and the endoplasmic reticulum-associated thyroid hormone-binding protein were easily detected from 0.5-1 x 10(4) cells by this method. Antibody as low as 10 ng/ml gave reproducible results. Using this method, the in vivo dynamic interconversion of monomer-tetramer of pyruvate kinase M2 was found to be regulated by glucose. The ligand-induced epidermal growth factor receptor through different subcellular compartments during endocytosis was easily quantified by this method. This method was also used to compare the different amounts of the endoplasmic reticulum-associated thyroid hormone-binding protein in various cultured cells. Thus, the in situ immunoassay is an easy and versatile method which can be used to study various cellular antigens and their involvement in cellular processes.

Animals↗

PubMed1992

[Short-term effects of Angelica sinensis and nifedipine on chronic obstructive pulmonary disease in patients with pulmonary hypertension].

UNLABELLED: 40 COPD cases with pulmonary hypertension (PH) in remission stage were equally divided into four groups, 10 cases in each. Group 1-4 were treated with 25% Angelica sinensis (250 ml, iv. drip, qd), nifedipine (10 mg, po, tid), both Angelica sinensis+nifedipine and blank control respectively. The study was designed to investigate the changes of hemodynamics, pulmonary function and blood gas before and after the treatments by impedance rheopneumogram, lung function examination and blood gas analysis. RESULTS: Mean pulmonary arterial pressure was decreased and cardiac output, PaO2 were increased significantly (P < 0.05 or P < 0.01) in group 3. The effects of group 3 appeared to be better than in other groups. The side effect of PaO2 lowering in group 2 was overcome in adding Angelica sinensis.

Aged↗