Biomedical subjects

S T Chen

Publications and source records attributed to S T Chen.

At least 91 records · Page 5Linked to original sources

PubMed1997

The role of the N-terminal leucine residue in snake venom cardiotoxin II (Naja naja atra).

The N-terminal leucine residue of snake venom cardiotoxin II (CTX II) (Naja naja atra) was systematically replaced with D-leucine (CTXII-L1-D-L), glycine (CTXII-L1G) or deleted [CTXII-(2-60)] to study the role of leucine residue in CTX II molecule. CTX II, CTXL1-D-L, CTXL1G and CTX(2-60) were produced by chemical synthesis method and purified by high performance liquid chromatography. Owing to folding problem in CTXII-(2-60), only CTX II, CTXII-L1-D-L and CTXII-L1G were produced in a pure form and characterized by amino acid analysis, mass spectrometry and peptide mapping. In the structural aspect, changing the Leu-1 by D-Leu or Gly causes a drastic alteration in the whole CTX II structure as detected by circular dichroism, 1-anilino-naphthalene-8-sulfonate (ANS) fluorescence assay. In the functional aspect, both CTXII-L1-D-L and CTXII-L1G are still retained substantial biological activity of CTX II. Therefore, the results indicate that both the chirality and the side-chain of the N-terminal leucine residue of CTX II are important elements in maintaining the whole CTX II structure. In addition, this study is the first report in elucidating the reason why the first N-terminal residue of most CTXs (90.3%) is leucine residue.

Amino Acids↗

PubMed1997

Expression of beta-amyloid precursor protein immunoreactivity in the retina of the rat during normal development and after neonatal optic tract lesion.

Immunoreactivity to beta-amyloid precursor protein (APP) was present in the inner plexiform, ganglion cell and optic fibre layers, as well as in blood vessels, at birth in normally developing rat retinas. In the inner plexiform layer immunoreactivity disappeared by postnatal day (P) 14. A small population of ganglion cells was immunoreactive at birth, but none were visible at P7. From P14 onwards, however, there was weak immunoreactivity in ganglion cells again, and strong staining in Müller glia. Retinas affected by neonatal optic tract lesions contained more immunoreactive ganglion cells at P4 than did controls, but by P14 there was a severe loss of ganglion cells. These observations are consistent with APP being involved in retinal differentiation, including maturation of glia and neurones, synaptogenesis and possibly neuronal survival.

Aging↗

PubMed1997

Myasthenia gravis and Charcot-Marie-Tooth disease type 1A: an unusual combination of diseases.

Concurrence of myasthenia gravis (MG) and Charcot-Marie-Tooth type 1 (CMT1A) neuropathy is rare. We describe a 60-year-old woman with MG and genetically proved CMT1A. The fluctuating ocular symptoms and proximal limb weakness were markedly improved by pyridostigmine treatment. Recognition of the possible association of MG and CMT1A in the same patient is important because the therapeutic result is rewarding.

Charcot-Marie-Tooth Disease↗

PubMed1997

Extracranial distal aneurysm of posterior inferior cerebellar artery.

An unusual aneurysm arising from an extracranial lateral medullary segment of the posterior inferior cerebellar artery (PICA) is reported. The origin of the PICA was also extracranial, 10 mm below the foramen magnum. The aneurysm was not seen on three-vessel angiography. The literature is reviewed with regard to the clinical and radiological features of such aneurysms. Occipital and nuchal headache with an altered level of consciousness, intraventricular haemorrhage, and hydrocephalus are suggestive of such aneurysm. The need for four-vessel angiography is again stressed.

Adolescent↗

PubMed1997

Klebsiella meningitis in Taiwan: an overview.

Klebsiella infection has been considered to be an uncommon cause of meningitis. To determine its incidence and clinical features, we reviewed the microbiologic records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted between 1981 and 1995. Klebsiella meningitis was diagnosed in 79 patients with 83 episodes. All patients had klebsiella isolated from CSF and/or blood and typical symptoms and signs of acute bacterial meningitis. Of these, 74 were over 16 years of age and 2 of the 5 children were infants. There was an increased prevalence rate of klebsiella meningitis after 1986. Of the 83 episodes, only 9 occurred between 1981 and 1986, accounting for 7.8% of 115 cases with CSF and/or blood culture-proven acute bacterial meningitis, whereas in 1987-95, there were 74 episodes accounting for 17.7% of 419 bacteriologically proven cases. K. pneumoniae accounted for 69 episodes, K. oxytoca, 11 episodes and K. ozaenae, 3 episodes. Male gender, diabetes mellitus and liver cirrhosis were commonly associated with K. pneumoniae meningitis. Neurosurgical procedures were frequently associated with K. oxytoca meningitis. All three patients with K. ozaenae meningitis had a primary disease of the nasopharyngeal pathway. The mortality rate due to K. pneumoniae was 48.5%, K. oxytoca, 10% and K. ozaenae, 0%. In patients with K. pneumoniae meningitis, poor prognostic factors included age over 60 years, diabetes mellitus, bacteremia and severe neurological deficits on the first day of treatment.

Adolescent↗

PubMed1997

Factor structure and age effects with an aphasia test battery in normal Taiwanese adults.

This study was designed to explore in a Taiwanese sample the factor structure of an aphasia test battery composed of parts of several standardized aphasia tests. A secondary goal was to assess effects of normal aging on the obtained factors. The sample was 120 healthy Taiwanese adults, ranging in age from 30 to 78 years. Principal-components analysis of the aphasia test battery revealed 5 factors: verbal comprehension, effortful writing, word production, automatized writing, and visuomotor coordination skills. Because the latter 2 factors have common psychological features, they can be combined and reinterpreted as a factor on the mechanics of writing. Further data analysis with factor scores shows that aging unfavorably influences verbal comprehension, effortful writing processing, and word production functions.

Adult↗

PubMed1997

Kinetic studies of the inhibitory effects of propeptides subtilisin BPN' and Carlsberg to bacterial serine proteases.

The propeptides of bacterial subtilisin BPN' and Carlsberg were synthesized to investigate their inhibitory function on the enzymes. Kinetically, pro-BPN' inhibits the proteolytic activities of subtilisin BPN' and Carlsberg separately in a slow binding mode. Pro-Carlsberg behaves as a typical rapid equilibrium competitive inhibitor for these two proteases. Functionally, pro-Carlsberg inhibits the subtilisins with moderate selectivity. The inhibition constant Ki of pro-BPN' to subtilisin BPN' is 5.0 nM, and 6.1 nM to subtilisin Carlsberg. The on-rate of pro-BPN' to subtilisin BPN' is 5.8 x 10(5) M(-1)s(-1), and the off-rate 2.9 x 10(-3) s(-1). Similarly, the on-rate of pro-BPN' to subtilisin Carlsberg is 2.2 x 10(5) M(-1)s(-1), and the off-rate 1.3 x 10(-3) s(-1). On the other hand, the Ki of pro-Carlsberg to subtilisin BPN' gives 1.3 x 10(2) nM, and 88 nM to subtilisin Carlsberg. Based on the key features of the interactions between pro-BPN' and subtilisin from X-ray crystallographic results (Gallagher et al., 1995), the correlation between the sequence of subtilisin propeptides and their inhibition abilities on the proteases are compared and discussed.

Amino Acid Sequence↗

PubMed1997

NMR and circular dichroism studies on the conformation of a 44-mer peptide from a CD4-binding domain of human immunodeficiency virus envelope glycoprotein.

Two-dimensional NMR, circular dichroism (CD) experiments and molecular modeling were performed to study the secondary structure of a 44-mer peptide fragment derived from the C4 region of gp120 of human immunodeficiency virus in aqueous solution. It was found a nascent helical structure exists following a type I turn near the N-terminus of the peptide. The proline residue in the turn appears to serve as a helix initiator. The helical structure was in fast dynamic equilibrium with beta- or random coil form on the NMR scale. A reverse turn was identified at a section containing two consecutive proline residues. A nascent helical structure has been detected for the region near the C-terminus of the 44-mer peptide. Higher helical content for the peptide is also indicated by CD studies on TFE titration. Thus it is proposed that, in more apolar medium, the Pro-Pro turn and the segment amino-terminal to it, spanning about 20 amino acids, may be converted into helix structure. Moreover, the region near the C-terminus of the peptide may also be induced into helix, so that a helix-turn-helix structure may be formed in the C4 domain of gp120. A helical wheel representation of this stretch shows amphipathicity of the helix. The biological implication of the conformational adaptibility of the peptide was discussed.

Amino Acid Sequence↗

PubMed1997

Guillain-Barré syndrome in Taiwan: a clinical study of 167 patients.

OBJECTIVE: To identify clinical characteristics of various forms of Guillain-Barré syndrome in Taiwan. METHODS: The clinical and electrophysiological data of 167 consecutive patients with Guillain-Barré syndrome admitted to Chang Gung Memorial Hospital, a general paediatric and adult hospital in Taiwan, were reviewed. RESULTS: Analysis of age distribution disclosed a high incidence (21%) among patients under the age of 10 years. Seasonal preponderance in Spring (March to May) was found. Utilizing clinical and electrophysiological data, these 167 patients with Guillain-Barré syndrome were subclassified; 82 (49%) had acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 32 (19%) had Fisher syndrome (FS), and six (4%) had axonal forms of Guillain-Barré syndrome. The remaining 47 (28%) patients were unclassified. Patients with AIDP and FS had many common clinical features, including seasonal distribution, history of preceding illness, sensory abnormalities, cranial nerve involvement except for extraocular motor nerves, and albuminocytological dissociation on examination of CSF. Follow up study on 145 patients disclosed that 127 (87%) recovered satisfactorily, 14 (10%) were persistently disabled, and four (3%) died during admission to hospital. Clinical features associated with poor outcome (persistent disability or death) were requirement for mechanical ventilation, a low mean compound muscle action potential amplitude (< or = 10% of the lower limit of normal), and age greater than 40 years. CONCLUSION: Guillain-Barré syndrome in Taiwan showed a peculiar age and seasonal distribution and a high frequency of FS not seen in other series. Given that patients with AIDP and FS had many common clinical features, AIDP and FS may have similar underlying pathological mechanisms.

Adolescent↗

PubMed1997

Dominant negative activity of mutant thyroid hormone alpha1 receptors from patients with hepatocellular carcinoma.

Complementary DNAs for two mutant thyroid hormone alpha1 receptors (TR alpha1) were isolated from hepatocellular carcinomas of two patients. Sequence analyses of the complementary DNAs showed a single Val390Ala and double Pro398Ser/Glu350Lys mutations in mutants H and L, respectively. We characterized their hormone-binding, DNA-binding, and dominant negative activities. Mutants H and L did not bind the hormone T3. Their DNA-binding activities were analyzed using three types of thyroid hormone response elements (TREs) in which the half-site binding motifs are arranged in an everted repeat (Lys), an inverted repeat (Pal), or a direct repeat separated by four nucleotides (DR4). Compared with wild-type TR alpha1 (w-TR alpha1), which bound these TREs with different homodimer/monomer ratios, binding of mutant L to the three TREs as homodimers was reduced by approximately 90%. However, binding of mutant H to these TREs was more complex. Although it bound normally to DR4 as homodimers, its binding to Lys as homodimers was reduced by approximately 80%. Surprisingly, its binding to Pal was markedly enhanced compared with w-TR alpha1. The binding of these two mutants to the three TREs as heterodimers with retinoid X receptors (RXR alpha and -beta) was not significantly affected. Consistent with the lack of T3-binding activity, both mutants had lost their trans-activation capacity. Mutants H and L exhibited dominant negative activity, but differed in their TRE dependency. The dominant negative potency of mutant H was in the rank order of Pal > DR4 > Lys, whereas no TRE dependency was observed for mutant L. The present study indicates that mutations of the TR alpha gene do occur in patients and that these novel TR alpha1 mutants provide a valuable tool to further understand the molecular basis of the dominant negative action of mutant TRs.

Base Sequence↗

PubMed1996

Local application of anti-NGF blocks the collateral sprouting in rats following chronic constriction injury of the sciatic nerve.

Systemic administration of anti-nerve growth factor (NGF) antibodies can block nociceptive fiber sprouting into denervated adult rat skin. However, the effect of local application of anti-NGF on collateral sprouting in rats caused by chronic constriction injury (CCI) has not been well studied. We investigated the influence of local anti-NGF on collateral sprouting caused by CCI of the rat's sciatic nerve. Using a dye-labeled plasma extravasation technique, we can easily evaluate the extent of collateral sprouting by the clearly defined blue coloration area. Our results showed that local application of anti-NGF either in a high or low dose significantly prevented the spread of collateral sprouting from the saphenous nerve into the sciatic innervation territory. In contrast, distilled water did not show a significant block of the saphenous nerve collateral sprouting. Our study suggests that collateral sprouting is dependent on the local availability of NGF by the nearby intact cutaneous nerve fibers.

Animals↗

PubMed1996

Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system.

We have previously shown that the G protein of vesicular stomatitis virus (VSV-G) can be incorporated into the virions of retroviruses. Since expression of VSV-G is toxic to most mammalian cells, development of stable VSV-G packaging cell lines requires inducible VSV-G expression. We have modified the tetracycline-inducible system by fusing the ligand binding domain of the estrogen receptor to the carboxy terminus of a tetracycline-regulated transactivator. Using this system, we show that VSV-G expression is tetracycline-dependent and can be modulated by beta-estradiol. Stable packaging cell lines can readily be established and high-titer pseudotyped retroviral vectors can be generated upon induction of VSV-G expression.

3T3 Cells↗

PubMed1996

Kinetic resolution of amino acid esters catalyzed by lipases.

Racemic amino acids were resolved by lipase via hydrolysis of their esters. Lipases (Pseudomonas lipase from Amano PS, Rhizopus lipase from Serva, and porcine pancrease lipase from Sigma) could selectively hydrolyze the L-amino acid esters in aqueous solution with high reactivities and selectivities. The effect of the structural changes in the ester moiety on the stereoselectivity of the lipases was also investigated using D,L-homophenylalanine as a model. Procedures were developed for the resolution of natural and unnatural amino acids.

Amino Acids↗

PubMed1996

Bacterial meningitis in patients with nasopharyngeal carcinoma.

Bacterial meningitis was found in 12 patients with nasopharyngeal carcinoma, accounting for 0.65% of the 1850 patients with the tumour diagnosed between 1981 and 1994 in our hospital. In 11 patients, the time-lag between diagnosis of cancer and the appearance of infection ranged from 9 months to 11 years (mean 57 months) whereas in one patient it was only 5 days. Three patients developed mixed bacterial meningitis. Cerebrospinal fluid culture for bacteria was positive in six patients. Three patients (25%) were bacteraemic. Gram-negative bacilli, especially Pseudomonas aeruginosa, were the most common pathogens. Age, sex and histopathology were not risk factors for infection. Conditions predisposing to meningitis included intracranial invasion of the tumor, neutropenia, otitis media, and neurosurgical procedures. All but two patients had intracranial tumour invasion and erosion of the base of the skull. Local spread of micro-organism to the meninges was more important than haematogenous spread. The overall mortality in our patients was 66.7%, much higher than in patients without cancer.

Adult↗

PubMed1996

Inducible gene expression by retrovirus-mediated transfer of a modified tetracycline-regulated system.

The ability to regulate gene expression via exogenous stimuli will facilitate the study of gene functions in mammalian cells. In the present study, we modified the tetracycline-controlled inducible system by the addition of the ligand-binding domain of the estrogen receptor to the carboxy terminus of the tTA transactivator. A single retroviral vector can transduce both the transactivator gene and the gene of interest controlled by the tTA-inducible promoter into mammalian cells. We show that cell lines expressing the transactivator can readily be established and that expression of the gene of interest depends on the removal of tetracycline and the addition of estrogen. By using this system, cell lines with inducible expression of the G protein of vesicular stomatitis virus, a potentially toxic gene product, were established. The combination of a powerful inducible system and retrovirus-mediated gene transfer can not only be used to study gene function but may also be applied in the future to clinical trials in human gene therapy.

Cell Line↗

PubMed1996

Identification of naturally occurring dominant negative mutants of thyroid hormone alpha 1 and beta 1 receptors in a human hepatocellular carcinoma cell line.

To understand the function of thyroid hormone nuclear receptors (TRs) in human hepatocellular carcinoma cells (HCC), we characterized the hormone binding and transactivational activity of TRs in a HCC cell line, J7. TR alpha 1 (J7-TR alpha 1) and TR beta 1 (J7-TR beta 1) complementary DNAs were cloned from this cell line, and the binding activity to the hormone response elements (TREs) and to the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3) of the expressed TR proteins were evaluated. J7-TR alpha 1 and J7-TR beta 1 bound to TREs similarly as the TRs isolated from other tissues. However, J7-TR alpha 1 did not bind to T3, and J7-TR beta 1 bound to T3 with only about 10% the affinity of the wild-type TR beta 1. Sequencing of the complementary DNAs shows a single Met259Ile mutation in J7-TR alpha 1 and Met334Val in J7-TR beta 1. Using reporters containing TREs, we found that J7-TR alpha 1 and J7-TR beta 1 had virtually lost their transactivational activity. Moreover, these two mutants inhibited the transactivational activity of the wild-type TRs by a dominant negative effect not only on the transfected TRs, but also on endogenous TRs in other two HCC cell lines, SK-Hep-1 and HepG2. The potency of the dominant negative effect of these two mutants inversely correlated with the expression level of endogenous TRs. The present studies identified two novel naturally occurring TR mutants that have potent dominant negative action. The identification of both the alpha and beta dominant negative mutants in J7 made this cell line a useful model system to further understand the molecular mechanism of the dominant negative action of TR mutants.

Carcinoma, Hepatocellular↗

PubMed1996

A longitudinal study of multimodal evoked potentials in patients following radiotherapy for nasopharyngeal carcinoma.

Radiation rhombencephalopathy and radiation myelopathy may occur in patients months or years after radiotherapy for malignancy of the head and neck. We obtained multimodal evoked potentials longitudinally in 26 patients with proven nasopharyngeal carcinoma. Recordings were made before radiotherapy and at 1 week, 3 months, 9 months, 15 months, and 24 months after radiotherapy. All absolute latencies of evoked response before and after radiation were within normal limits. However, the I-III interpeak latencies of brainstem auditory evoked potentials and the onset latencies of motor evoked potentials in the whole group of patients at 15 months after radiation were significantly longer than those before radiotherapy, whereas the latencies at 24 months were not significantly different. The N20 latencies of somatosensory evoked potentials after radiotherapy were significantly prolonged at 3 months of follow-up; the prolongation then became normal. They indicate that a subclinical reversible radiation-induced dysfunction may occur in the auditory, sensory, and motor systems.

Adult↗

PubMed1996

Tuberculous meningitis in patients with nasopharyngeal carcinoma.

Mycobacterial infection has been recognized as a complication in patients with malignancy. Tuberculous (TB) meningitis has not been reported in patients with nasopharyngeal carcinoma (NPC); it may have been overlooked or confused with the underlying malignancy or meningitis caused by other microorganisms. We describe the occurrence of culture-proven TB meningitis in 2 NPC patients. The time lag between the diagnosis of NPC and the occurrence of TB meningitis was 4 years in 1 patient and 6 years in the other. In both patients, the diagnosis of TB meningitis was delayed; they were initially treated for bacterial meningitis. Subsequent antituberculous chemotherapy was successful in 1 patient but failed in the other. Recognition of the infection is important for early diagnosis and proper treatment of this potentially fatal condition in patients with NPC.

Antineoplastic Combined Chemotherapy Protocols↗