Biomedical subjects

S T Chen

Publications and source records attributed to S T Chen.

At least 127 records · Page 7Linked to original sources

PubMed1995

Fabry's disease: report of a case.

Fabry's disease is a rare hereditary disorder of glycosphingolipid metabolism. Its clinical features have not been adequately described in Taiwan. This paper reports on a 32-year-old man who had painful acroparesthesia, disseminated skin angiokeratomas, whorled corneal opacity, mitral valve prolapse and renal insufficiency. There was also involvement of the central motor pathways and the autonomic nervous system. A sural nerve biopsy showed loss of small myelinated and unmyelinated fibers. A reduced serum activity of alpha-galactosidase A and a large amount of urinary globotriaosylceramide confirmed the diagnosis of Fabry's disease.

Adult↗

PubMed1995

Inhibition of protein kinase C by snake venom toxins: comparison of enzyme inhibition, lethality and hemolysis among different cardiotoxin isoforms.

Cardiotoxins, neurotoxins and phospholipase A2 (PLA2) are three major classes of toxic components present in the Taiwan cobra, Naja naja atra of the Elapidae family. Cardiotoxins (or called cytotoxins), a group of major polypeptides of around 60 amino-acid residues present abundantly in the elapid family of snakes, comprise about 45-55% of the crude venom of Taiwan cobra. In contrast to another prominent group of structurally similar neurotoxins with well-established acetylcholine receptors and modes of action, cardiotoxins showed no defined cellular targets and very diverse pharmacological functions. A systematic structure/function comparison of these toxins was made by their relative inhibitory effects on protein kinase C (PKC) isolated from mouse brains. Lethality and hemolysis of various cardiotoxin isoforms were also compared in order to shed some insight on the biological targets and mechanisms of these surface-active amphiphilic polypeptides. A structure comparison of these cardiotoxins based on computer model-building revealed that some defined and subtle differences can be detected upon the superposition of these three-dimensional polypeptide chains, which may reflect the intrinsic differences in the hydrophobic peptide segments present on the surface loops of toxin molecules. The differences seem to correlate with different inhibitory activities exhibited by cardiotoxins in contrast to the lack of activity by cobrotoxin and PLA2 on PKC.

Animals↗

PubMed1995

Elucidation of the insurmountable nature of an angiotensin receptor antagonist, SC-54629.

SC-54628 [1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H- tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one] and its 1-(2,6-dimethylphenyl)-2H-imidazol-2-one derivative SC-54629 were potent inhibitors of 125I-angiotensin II (125I-AII) binding to rat adrenal cortex angiotensin type 1 (AT1) receptors. SC-54628 and SC-54629 antagonized AII-induced contraction of rabbit vascular smooth muscle in a surmountable fashion and an insurmountable fashion, respectively. Binding experiments with SC-54629 were undertaken to determine the nature of receptor interaction, which might explain the insurmountable mode of antagonism of SC-54629. The presence of a high concentration of SC-54629 did not affect the dissociation of membrane-bound 125I-AII induced by an excess of unlabeled AII, indicating that the antagonist binds to the agonist binding site and not an allosteric domain. Incubation of adrenal cortex membranes with SC-54629 decreased the density of 125I-AII binding sites. When incubation of the SC-54629-treated membranes with radiolabeled AII was prolonged, the SC-54629-induced decrease in AT1 receptor density was attenuated, suggesting that binding of the antagonist is slowly reversible. Furthermore, the dissociation of [3H]SC-54629 was 5-fold slower than that of 125I-AII bound to AT1 receptors. These results suggest that the insurmountable antagonism of AII by SC-54629 is most likely due to the slow reversibility of SC-54629 binding to the AT1 receptor.

Angiotensin II↗

PubMed1995

Rimmed, vacuolar distal myopathy in two Taiwanese siblings.

Distal myopathy with rimmed vacuoles (DMRV) is a rare disease that has not previously been reported in Taiwan. This paper reports two siblings with DMRV. Each showed a different pattern of disease progression, one being slowly and the other rapidly progressive. Both patients' initial symptoms appeared in early adulthood, manifesting as muscular wasting and weakness of the legs, especially in the distal muscles. Severe generalized involvement of skeletal muscles, with sparing of the facial, extraocular, bulbar, intercostal and diaphragm muscles was recognized in the advanced stage. The striking finding in their muscle biopsy specimens was the presence of "rimmed" vacuoles. Magnetic resonance imaging showed more severe involvement of the anterior compartment muscles of the lower legs. DMRV is thought to be inherited as an autosomal recessive trait and is distinguishable from other types of distal myopathy on the basis of clinical and pathologic findings. The literature on the subject is reviewed with emphasis on the differences between distal myopathic syndromes.

Adult↗

PubMed1994

Bcl-2 proto-oncogene protein immunoreactivity in normally developing and axotomised rat retinas.

This study demonstrates immunocytochemically that bcl-2 (B cell lymphoma) proto-oncogene protein is expressed by two populations of retinal cells, one in the inner retina representing developing neurons or glia at perinatal stages, and the other identified as Müller cells from postnatal day 10 onward. An increase in bcl-2 immunoreactivity was detected in the Müller cell processes after neonatal optic tract lesion or optic nerve transection in adult rats. These results suggest that bcl-2 protein may function on cellular differentiation, maturation and homeostasis in the inner retina, and its expression by Müller cells can be up-regulated by the degeneration of ganglion cells.

Animals↗

PubMed1994

Protein gene product 9.5-immunoreactive retinal neurons in normal developing rats and rats with optic nerve or tract lesion.

The present immunocytochemical study indicates that protein gene product 9.5 (PGP 9.5) in the rat retina first appears in a population of neurons in the inner and central part of the neuroblast layer at embryonic day (E) 14. Presumptive horizontal cells which are PGP 9.5 positive were observed at E17. At birth, cells in the inner nuclear layer and ganglion cell layer (GCL) as well as the inner plexiform layer (IPL) were positive. Further differentiation, particularly the appearance and the formation of immunoreactive sublaminae in the IPL, was observed in the first 2 postnatal weeks. This pattern reached adult levels by postnatal day 14. In rats with unilateral neonatal optic tract lesion or optic nerve transection as young adults, 43-45% of the immunoreactive cells were lost in the GCL. However, only minor changes were detected in the IPL, suggesting that amacrine cells contribute mainly to the PGP 9.5 immunoreactivity in this laminar zone of the retina.

Aging↗

PubMed1994

Deletion of chromosome arm 1p in a Merkel cell carcinoma (MCC).

A case of neuroendocrine skin carcinoma (Merkel cell carcinoma) with a deletion of the short arm of chromosome 1 (1p) as the sole chromosomal abnormality was examined. The tumor originated in the skin of the left knee of a 67-year-old man. Histopathologic study showed an undifferentiated small cell tumor which expressed neuron-specific enolase, chromogranin, and cytokeratin (CAM 5.2). Cytogenetic analysis of a lymph node metastasis from the groin showed a pseudodiploid cell population with a deletion of the short arm of chromosome 1 as the only abnormality: 46,XY,del(1)(p36.1). In situ hybridization with the D1Z2 probe specific for the terminal band of 1p confirmed the terminal deletion. This is the first case of Merkel cell carcinoma in which only one chromosomal abnormality has been observed. Loss of the terminal portion of 1p suggests that a tumor suppressor gene on 1p plays a role in the pathogenesis of Merkel cell carcinoma.

Carcinoma, Merkel Cell↗

PubMed1994

Citrobacter meningitis in adults.

Citrobacter meningitis is an uncommon infection of neonates and young children. It is rarely seen in adults. We describe a 46-year-old man with a mixed bacterial meningitis caused by C. diversus and Klebsiella oxytoca and a 64-year-old woman with C. freundii meningitis. Review of the English-language literature revealed only 2 adult patients with C. diversus meningitis and another 2, with C. freundii meningitis. The ages of these 6 aforementioned patients ranged from 31 to 84 years. Multiple facial fractures, neurosurgical procedures, alcoholism and diabetes mellitus were predisposing conditions. Among the 5 patients whose outcome was known, antibiotic therapy was successful in 4 but failed in 1. This study emphasizes that almost any of the gram-negative bacilli can cause serious infection of the central nervous system in adults in the proper setting.

Adult↗

PubMed1994

Klebsiella pneumoniae meningitis: prognostic factors.

All 42 cases of Klebsiella pneumoniae meningitis diagnosed between 1981 and 1991 were evaluated. These accounted for 13% of patients with blood and/or cerebrospinal fluid culture-proven bacterial meningitis. There was an increased incidence of K. pneumoniae meningitis from the first 6 years of study (7%) to the last 5 years (16%). K. pneumoniae became increasingly important not only in community-acquired meningitis but also in nosocomial meningitis. 12/13 nosocomial cases were patients who had undergone neurosurgical procedures. The overall mortality rate was 43%. The mortality rate in patients with spontaneous meningitis was higher than that in patients with post-traumatic or postoperative meningitis. Factors that adversely affected mortality were age over 60, diabetes mellitus, and severe neurological deficits on admission. The use of third-generation cephalosporins did not reduce the mortality rate.

Adult↗

PubMed1994

Relapsing bacterial meningitis in adults.

Relapsing bacterial meningitis is a rare condition, diagnosed in eight patients between 1981 and 1993 at our institution. These accounted for 3.4% of 234 adult patients with blood and/or cerebrospinal fluid culture-proven bacterial meningitis. A review of the English-language literature from 1966 to the present revealed only five further adult cases of relapsing bacterial meningitis with in-depth case histories. Of these 13 total patients, nine were female and four male, aged 17-61 years. Ten were neurosurgical patients. Gram-negative bacilli, especially Klebsiella species, were the commonest micro-organisms identified for both the initial episode and the relapse of infection. Three patients died in the course of relapse. Four or more weeks of antibiotic therapy may be needed to treat post-surgical patients with Gram-negative bacillary meningitis. Even a normal cerebrospinal fluid study at the end of treatment of bacterial meningitis is not a guarantee of freedom from relapse.

Adult↗

PubMed1994

Nonsurgical treatment of spinal epidural abscess: report of a case.

Traditionally, the treatment of choice for spinal epidural abscess (SEA) is decompressive laminectomy and debridement followed by antibiotics. In recent years, nonsurgical treatment in selected cases has been reported. This report describes a 39-year-old man with lumbar SEA diagnosed by computed tomographic-myelography. In the absence of neurological deficit and the presence of infective endocarditis and a known pathogen, the patient received only antibiotic treatment and made an uneventful recovery.

Abscess↗

PubMed1994

Polymerase chain reaction in the diagnosis of chromosomal breakpoints.

Polymerase chain reaction-based methods for the detection of translocation-induced gene rearrangements are now widely used for diagnostics and patient monitoring. This article concentrates on two of the best studied chromosome translocations resulting in specific gene rearrangements and oncogene activation: the Philadelphia translocation of chronic myelogenous leukemia and acute leukemias, and the t(14;18) translocation of follicular lymphomas.

Chromosome Aberrations↗

PubMed1993

Conformation of a cyclic opioid peptide analog by NMR and molecular dynamics simulation.

The conformation of a new Ty-c[Lys-Phe-Asp]-NH2 cyclic opioid peptide synthesized by solid phase method, has been determined from two-dimensional NMR and distance geometry followed by restrained molecular dynamics simulation. The conformation of the ring is well-defined, but the exocylic Tyr-1 and Phe-3 side-chain moiety possesses significant orientational freedom.

Amino Acid Sequence↗

PubMed1993

Mutational analysis of hepatitis B virus enhancer 2.

Hepatitis B virus (HBV) infection is associated with the development of hepatocellular carcinoma in humans. HBV infection is primarily restricted to hepatocytes, and replication and gene expression of HBV require liver-specific transcription factors. Regulation of HBV gene expression has been shown to be controlled by two enhancers, and liver-specific gene expression of HBV can be attributed largely to the activity of enhancer 2. In this study, we have used mutational analysis to identify a 20-base-pair sequence motif essential for the liver-specific enhancer 2 activity. Analysis of the sequence reveals that this motif is similar to the regulatory region of several other liver-specific cellular genes, suggesting that common transcription factors may be involved in the activation of cellular as well as HBV gene expression in hepatocytes.

Base Sequence↗

PubMed1993

Monoarthritis in the rat knee induces bilateral and time-dependent changes in substance P and calcitonin gene-related peptide immunoreactivity in the spinal cord.

Bilateral changes in the spinal cord and dorsal root ganglion content of the sensory peptides substance P and calcitonin gene-related peptide have been previously reported in animal models of arthritis which affect many joints within the body. The central nervous system has been implicated in the symmetry of joint involvement in human rheumatoid arthritis. We aimed to determine whether unilateral inflammation of the knee joint can also induce bilateral changes in the spinal cord. We have induced a monoarthritis in the knee joint of the rat and used quantitative immunocytochemistry to look at changes of these peptides in the dorsal horn of the spinal cord and the dorsal root ganglia. Furthermore we have examined the responses during the acute (three days) and the chronic (21 days) phases of the model. The data show that in the acute phase of the monoarthritis there is both an ipsilateral and contralateral response which increases the immunoreactive substance P and calcitonin gene-related peptide in the L4 level of the dorsal horn of the spinal cord. In the chronic phase of the monoarthritis, the contralateral side of the dorsal horn returned to control values whilst the ipsilateral side showed reduced amounts of immunoreactive substance P and calcitonin gene-related peptide compared to controls. We propose that the acute response, at three days, to unilateral inflammation is appropriate and has evolved to protect an organism against the original insult ipsilaterally, and the possibility of subsequent insult contralaterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Investigating the s-2 subsite selectivity of alkaline proteases in hydrolysis of diastereo-peptide esters and molecular-modeling interpretation.

Diastereomeric peptide-esters (Ala-Ala-AA2-Phe-OMe, AA2 = Gly, D- or L-Ala, Pro, Phe, Lys, and Glu) have been used as substrates, and the kinetic constants (Kcat and Km) of the three alkaline proteases, subtilisin Carlsberg, alcalase, and Nagarse (subtilisin BPN') catalyzed ester-hydrolysis, were measured to investigate the selectivity of the enzyme-catalyzed peptide esterhydrolysis. All three proteases preferred the substrate which had a small side-chain at the s-2 site. Thus, the substrates with a bulky side-chain at the p-2 site such as Phe, Pro, Glu, and Lys, hydrolyzed with a rate of about one-tenth that of Ala at the p-2 site, and the Kcat decreased as the size of the p-2 amino acid residue increased. The diastereoselectivity of the alkaline protease-catalyzed hydrolysis of each diastereomeric pair depended on the size of the amino acid residue at the p-2 position of the substrate. The substrates with a bulky side-chain at the p-2 site hydrolyzed with higher diastereoselectivity than did the substrates with a small side-chain at the p-2 site. Molecular modeling of the enzyme-substrate complex show that: for the enzyme complexed with a substrate which has L-L-L-L configuration, each residue of the L-L-L-L tetrapeptide filled in and was completely enclosed by the cleft of the four subsites of the enzyme. The side-chains of the residues were identically positioned within the pocket of the binding-site. For the complex of enzyme with substrate of L-L-D-L, the side-chain of the D-amino acid residue was far away from the s-2 subsite of the enzyme, and had close contact with the side-chains of Leu-126 and Ile-107 of the enzyme.

Amino Acid Sequence↗

PubMed1993

Highly efficient elimination of Philadelphia leukemic cells by exposure to bcr/abl antisense oligodeoxynucleotides combined with mafosfamide.

Synthetic oligodeoxynucleotides complementary to the break-point junction of bcr-abl transcripts selectively inhibit the proliferation of Philadelphia-positive leukemic cells, but residual leukemic cells persist in antisense oligodeoxynucleotides-treated cultures. Cyclophosphamide derivatives such as mafosfamide and 4-hydroperoxycyclophosphamide are used at high doses for purging of Philadelphia leukemic cells from marrows but such treatment can be associated with delayed engraftment and prolonged cytopenias. To develop a more effective procedure that might optimize the killing of leukemia cells and the sparing of normal hematopoietic progenitor cells, a 1:1 mixture of Philadelphia leukemic cells and normal bone marrow cells was exposed to a combination of a low dose of mafosfamide and bcr-abl antisense oligodeoxynucleotides and assayed for growth ability in clonogenic assays and in immunodeficient mice. Bcr-abl transcripts were not detected in residual colonies, and cytogenetic analysis of individual colonies revealed a normal karyotype. Normal but not leukemic hematopoietic colonies of human origin were also detected in marrows of immunodeficient mice 1 mo after injection of the treated cells. Our results indicate that a combination of a conventional chemotherapeutic agent and a tumor-specific antisense oligodeoxynucleotide is highly effective in killing leukemic cells and in sparing a much higher number of normal progenitor cells as compared with high-dose mafosfamide treatment. This offers the prospect of a novel and more selective ex vivo treatment of chronic myelogenous leukemia.

Animals↗

PubMed1993

Carotid ultrasonographic findings in intracranial internal carotid artery occlusion.

Five cases of unilateral intracranial internal carotid artery (ICA) occlusion received both carotid angiographic and ultrasonographic studies. The Doppler examination showed that the resistive index (RI) of the common carotid artery (CCA) and ICA was higher but the peak systolic velocity was lower on the diseased side as compared with the normal side. Absence of the diastolic phase was found in the CCA flow in 2 cases and in the ICA flow in 3 cases on the diseased side. The mean CCA flow volume on the diseased side (271 +/- 82 mL/min) was half or less than that on the normal side (680 +/- 86 mL/min) (P < 0.01). The flow volume of the diseased ICA (49 +/- 20 mL/min) was markedly lower than that of the normal side (344 +/- 49 mL/min) (P < 0.01) and was also less than that of the ipsilateral external carotid artery (ECA) (129 +/- 43 mL/min). The Doppler ophthalmic artery flow all showed a forward direction. The authors propose that the following extracranial carotid ultrasonographic findings may be helpful in the prediction of intracranial carotid artery occlusion: (1) diminished frequencies, increased RI, and a more than 50% reduction of flow volume in the CCA as compared with the opposite side; (2) diminished frequencies to loss of the diastolic phase, a more than 50% reduction of the flow volume, and reversed ICA/ECA flow volume in the ICA as compared with the opposite side; and (3) a forward Doppler ophthalmic artery flow.

Adult↗