Biomedical subjects

S T Chen

Publications and source records attributed to S T Chen.

At least 73 records · Page 4Linked to original sources

PubMed1999

Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial?

Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.

Animals↗

PubMed1998

Chemical mechanism of the endogenous argininosuccinate lyase activity of duck lens delta2-crystallin.

The endogenous argininosuccinate lyase activity of duck delta2-crystallin was specifically inactivated by the histidine-specific reagent, diethyl pyrocarbonate. The protein was protected by l-citrulline or l-arginine from the diethyl pyrocarbonate inactivation. To characterize further the chemical mechanism of the delta2-crystallin-catalysed reaction, deuterium-labelled argininosuccinate was enzymically synthesized from fumarate and l-arginine with delta2-crystallin in 2H2O. The argininosuccinate synthesized contained about 19% of the anhydride form; however, the deuterium was clearly demonstrated to be incorporated enantioselectively. Only the pro-HR atom at C-9 of the succinate moiety was labelled in the [2H]argininosuccinate-9-d synthesized, which indicates an anti-elimination mechanism for the endogenous argininosuccinate lyase activity of delta2-crystallin. The enzymic activity of duck lens delta2-crystallin in the pH range 5.5-8.5 was investigated using both protium- and deuterium-labelled argininosuccinate as the substrate. From the logkcat versus pH plot, two molecular pKa values of 6.18+/-0.02 and 8.75+/-0.03 were detected in the delta2-crystallin-argininosuccinate binary complex. The former must be dehydronated and the latter hydronated to achieve an optimum reaction rate. The logkcat/Km versus pH plot suggested two molecular pKa values of 5.96+/-0.09 and 8.29+/-0.10 for the free delta2-crystallin to be involved in the substrate binding. Small kinetic isotope effects of 1.17+/-0.02 and 1.05+/-0.09 were found for kcat and kcat/Km respectively. Combining results from labelling and kinetic analysis indicates that the endogenous argininosuccinate lyase activity of duck delta2-crystallin is compatible with a stepwise E1cB mechanism, the rate-limiting step probably at the C-N bond-cleavage step.

Animals↗

PubMed1998

The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition.

Stably transfected Jurkat T cells were produced in which Bax expression is inducible by muristerone A. The cell death resulting from induction of the overexpression of Bax was prevented by inhibition of the mitochondrial permeability transition (MPT) with cyclosporin A (CyA) in combination with the phospholipase A2 inhibitor aristolochic acid (ArA). The caspase-3 inhibitor Z-Asp-Glu-Val aspartic acid fluoromethylketone (Z-DEVD-FMK) had no effect on the loss of viability. The MPT was measured as the CyA plus ArA-preventable loss of the mitochondrial membrane potential (DeltaPsim). The MPT was accompanied by the release of cytochrome c from the mitochondria, caspase-3 activation in the cytosol, cleavage of the nuclear enzyme poly(ADP-ribose)polymerase (PARP), and DNA fragmentation, all of which were inhibited by CyA plus ArA. Z-DEVD-FMK had no effect on the loss of DeltaPsim and the redistribution of cytochrome c but did prevent caspase-3 activation, PARP cleavage, and DNA fragmentation. It is concluded that Bax induces the MPT, a critical event in the loss of cell viability. In addition to the cell death, the MPT mediates other typical manifestations of apoptosis in this model, namely release of cytochrome c, caspase activation with PARP cleavage, and DNA fragmentation.

Apoptosis↗

PubMed1998

Genomic organization and characterization of the promoter region of the round-spotted pufferfish (Tetraodon fluviatilis) JAK1 kinase gene.

Seventeen kilobases of genomic DNA containing the promoter and the coding region of the round-spotted pufferfish JAK1 gene was isolated and completely sequenced. This gene consists of 25 exons and 24 introns spanning about 13.5 kb, compared to > 30kb in carp JAK1 gene. Primer extension analysis revealed one transcription initiation site which was 376 bp upstream of the translation initiation site. The sequence of the 2.9 kb region upstream of the transcription initiation site contains numerous potential binding sites for transcription factors including HNF-5, GCF, Sp1, CRE, AP2, GATA, GAGA, E2A, p53, and NF-IL6. When this region was placed upstream of the chloramphenicol acetyltransferase (CAT) reporter gene and transfected into a carp CF cell line, it could drive the synthesis of CAT enzyme three times more efficiently than could the common carp JAK1 promoter.

Animals↗

PubMed1998

Hypoplasia of the internal carotid artery with intercavernous anastomosis.

We report a symptomatic case of unilateral hypoplasia of the internal carotid artery with an intercavernous anastomosis, a very rare developmental anomaly. The symptoms were caused by occlusion of the proximal middle cerebral artery which possibly related to the haemodynamic stress caused by the anomalous intercavernous anastomosis.

Arteriovenous Anastomosis↗

PubMed1998

Growth status in children with cystic fibrosis based on the National Cystic Fibrosis Patient Registry data: evaluation of various criteria used to identify malnutrition.

OBJECTIVES: The objectives of this study were to determine growth status and to identify malnutrition with various anthropometric indicators in children with cystic fibrosis (CF) based on cross-sectional analysis of the 1993 National CF Patient Registry data. METHODS: Heights and weights of 13,116 children with CF were evaluated with percentile, percent of reference median, Z-score, and percent ideal weight-for-height based on National Center for Health Statistics/Centers for Disease Control growth references. Malnutrition was defined by four criteria: (1) height-for-age <5th percentile ("stunting") or weight-for-age <5th percentile ("wasting") (2) height-for-age <90% of reference median or weight-for-age <80% of reference median, (3) height-for-age <5th percentile or percent ideal weight-for-height <85%, and (4) height-for-age <90% of reference median or weight-for-height <85% of reference median. RESULTS: Mean and median height- and weight-for-age were found to be at the 30th and 20th percentiles in children with CF. Malnutrition (height- or weight-for-age <5th percentile) was particularly pronounced in infants (47%) and adolescents (34%) and patients with newly diagnosed CF (44%). A significant sex difference (p < 0.01) in the occurrence of stunting (height-for-age <5th percentile) was observed during adolescence: boys 11 to 14 years of age showed lower occurrence of stunting (19%) compared with girls (29%), whereas the opposite trend was observed at 15 to 18 years (34% in male patients vs 28% in female patients). CONCLUSION: Twenty percent of all children in the 1993 National CF Patient Registry were <5th percentile for height- or weight-for-age. A significant discrepancy was found when different criteria were used to distinguish "stunting" versus "wasting" in malnourished children with CF.

Adolescent↗

PubMed1998

Haemophilus influenzae meningitis in adults.

Haemophilus influenzae meningitis is rare in adults. We reviewed the microbiological records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted to Chang Gung Memorial Hospital from January 1978 to May 1996. Haemophilus influenzae meningitis was found in six adult patients, accounting for 1.8% of 326 bacteriologically proven adult cases of meningitis diagnosed between January 1984 and May 1996. Predisposing conditions included head trauma and/or neurosurgical procedure in four patients and an extracranial extension of a pituitary adenoma in a diabetic patient. None of them had altered consciousness on the day of treatment. A CSF cell count less than 500 x 10(6) leukocytes/liter was noted in three patients. Antibiotic therapy was successful in all patients. Thus, predisposing conditions, particularly head trauma and/or neurosurgical procedure, are commonly present in adult patients with H. influenzae meningitis. Patients with the infection may have a low cellular count in the CSF that may be readily misinterpreted as meningitis caused by other pathogens.

Adult↗

PubMed1998

Neuropsychological function in patients with nasopharyngeal carcinoma after radiotherapy.

A neuropsychological test battery was administered to 27 adult patients with nasopharyngeal carcinoma (NPC) who had received radiotherapy, 28 adult patients with NPC awaiting radiotherapy, and 35 normal adult controls. The 27 patients with radiotherapy had a conventional dosage, 220 cGy per fraction, or less. The median interval between the completion of radiotherapy and the evaluation of neuropsychological function was 1.7 years. Groups were matched for age and educational level. The results showed that our NPC group with radiotherapy had neuropsychological impairments in the areas of auditory attention/concentration, immediate and delayed verbal recall and immediate visual recall, and recent memory, higher-order visuospatial abilities, and bimanual dexterity. Thus neuropsychological dysfunction may occur in patients with NPC within the first 2 years after radiotherapy.

Adult↗

PubMed1998

Factors that affect the expression of beta-amyloid precursor protein immunoreactivity in the rat retina.

Expression of beta-amyloid precursor protein immunoreactivity in the rat retina was studied after intravitreal injection of substances known to influence neural function in different ways. The substances were the excitatory amino acid glutamate, the inflammatory agent lipopolysaccharide, the depolarizing agent potassium chloride, and the potassium channel blocker barium chloride. In comparison with controls, more beta-amyloid precursor protein immunoreactivity was observed in the radial process of Müller glial cells 24 hours after injection of glutamate or lipopolysaccharide. In contrast, administration of barium chloride greatly reduced immunostaining in Müller cells. Further, an increase in immunostaining was observed in the inner and outer plexiform layers in retinas treated with any of the 3 chemicals, and in blood vessels after injection of glutamate and lipopolysaccharide. These observations suggest that multiple but specific signaling pathways are involved in regulating expression of beta-amyloid precursor protein in distinct cell types and regions in the retina.

Amyloid beta-Protein Precursor↗

PubMed1998

In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an infectious form by the addition of the vesicular stomatitis virus surrogate envelope G protein.

In the absence of envelope gene expression, retrovirus packaging cell lines expressing Moloney murine leukemia virus (MLV) gag and pol genes produce large amounts of noninfectious virus-like particles that contain reverse transcriptase, processed Gag protein, and viral RNA (gag-pol RNA particles). We demonstrate that these particles can be made infectious in an in vitro, cell-free system by the addition of a surrogate envelope protein, the G spike glycoprotein of vesicular stomatitis virus (VSV-G). The appearance of infectivity is accompanied by physical association of the G protein with the immature, noninfectious virus particles. Similarly, exposure in vitro of wild-type VSV-G to a fusion-defective pseudotyped virus containing a mutant VSV-G markedly increases the infectivity of the virus to titers similar to those of conventional VSV-G pseudotyped viruses. Furthermore, similar treatment of an amphotropic murine leukemia virus significantly allows infection of BHK cells not otherwise susceptible to infection with native amphotropic virus. The partially cell-free virus maturation system reported here should be useful for studies aimed at the preparation of tissue-targeted retrovirus vectors and will also aid in studies of nucleocapsid-envelope interactions during budding and of virus assembly and virus-receptor interactions during virus uptake into infected cells. It may also represent a potentially useful step toward the eventual development of a completely cell-free retrovirus assembly system.

Animals↗

PubMed1998

Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: In vitro studies have shown that nerve growth factor (NGF) is protective to cortical neurons against various insults. However, the role of NGF in relation to its high-affinity trkA receptor in the cortical neurons has not been well discussed. In this experiment, we studied the possible involvement of the NGF/receptor system in the ischemic injury of cortical neurons after focal cerebral ischemia in rats. METHODS: Male Wistar rats received right middle cerebral artery occlusion of 90 minutes' duration. The rats were decapitated at different reperfusion time points: hour 4 and days 1, 3, 7, and 14 of recirculation. Brain sections at the level of striatum were immunostained against NGF, trkA, glial fibrillary acidic protein (GFAP), and stress protein HSP70. Double immunostaining against NGF and GFAP was also performed. Optical density of NGF immunoreactivity in the ischemic and nonischemic cortexes was compared between sham-control and ischemic animals. RESULTS: In the sham-control rats, NGF immunoreactivity was present in the cortical and striatal neurons. However, beginning at hour 4 after recirculation, there was a significant decrease of NGF in the ischemic cortex and striatum. Beginning at day 1, NGF was absent completely in the infarcted striatum and cortex. However, in the peri-infarct penumbra area, despite a decrease in NGF at hour 4 and day 1, NGF recovered beginning at day 3 and returned almost to the sham-control level at day 14. In the nonischemic cortex, NGF increased beginning at hour 4, peaked at day 7, and returned almost to the sham-control level at day 14. The trkA and HSP70 immunoreactivities were not present in the sham-control cortex. However, trkA was induced at hour 4 in the ischemic cortex and at days 1 and 3 in the peri-infarct penumbra cortex. The HSP70 was induced at days 1 and 3 in the peri-infarct penumbra area. Double immunostaining showed that the number of GFAP-positive cells increased gradually, and NGF immunoreactivity in the GFAP-positive cells became gradually intense after ischemia. CONCLUSIONS: Our study demonstrated a temporal profile of NGF and trkA in the ischemic cortex and NGF expression by reactive astrocytes. Our data suggest that the NGF/receptor system may play a role in the astrocyte/neuron interaction under certain pathological conditions, such as focal cerebral ischemia.

Animals↗

PubMed1998

Executive dysfunction in Alzheimer's disease: association with neuropsychiatric symptoms and functional impairment.

Relationships between measures of executive skills and neuropsychiatric and functional status were examined in a group of 31 patients with Alzheimer's disease. Deficits in four executive skills tests were significantly associated with the Agitation/Disinhibition factor score and Total Neuropsychiatric score on the Neurobehavioral Rating Scale, as well as the Activities subscore on the Blessed Dementia Scale. The majority of these associations remained significant after covariance for Mini-Mental State Examination scores. Executive dysfunction is associated with clinically relevant neuropsychiatric symptoms and functional impairment in Alzheimer's disease. These associations may be independent of other cognitive deficits such as memory, language, and visuospatial skills, and may not be appreciated on routine clinical evaluations. Executive skills deficits, neuropsychiatric symptoms, and functional disability may emerge from shared neurobiological mechanisms.

Aged↗

PubMed1998

Bipolar disorder in late life: a review.

Although there is a broad base of literature on depression among elderly patients and on mania in younger patients, there is a relative paucity of information on bipolar disorder in the elderly population. While the quantities of data reflect the relative prevalences of these illnesses, there is evidence to suggest that classification of mania in the elderly with respect to age of onset, natural course, family history, and pathophysiology may be useful in understanding the heterogeneous etiologies of this syndrome. This paper presents a review of the literature on the incidence and course of illness in late-life bipolar disorder. Further, dilemmas of diagnostic classification in relation to associated risk factors will be discussed.

Age of Onset↗

PubMed1998

Immunoreactivity to synaptosomal-associated protein-25 in developing rat retinas: effects of a glutamate agonist and retinal transplantation to a host brain.

In the postnatal rat retina immunoreactivity to synaptosomal-associated protein-25 (SNAP-25) was expressed primarily in the photoreceptors, inner and outer plexiform layers, and optic nerve fibres in a highly specific and age related manner. Of special interest are observations of characteristic changes of intracellular immunostaining in photoreceptors and distinct immunoreactive sublaminae in the inner plexiform layer during early postnatal stages. The overall pattern of immunoreactivity in the photoreceptor and plexiform layers remained unchanged after neonatal intravitreal injection of the glutamate agonist 2-amino-4-phosphonobutyric acid or optic tract lesion, and after adult intraorbital optic nerve section. However, a significant reduction in immunostaining in the inner plexiform and optic nerve fibre layers was observed several weeks after transplantation of the retina to a neonatal host brain. These results provide new insights into the role of SNAP-25 in membrane remodelling in relation to specific cell types and functions, and into intraretinal regulatory mechanisms that seem to be independent of the levels of glutamate and the influence of retinal ganglion cells.

Aminobutyrates↗

PubMed1998

Periodontics and its influence on aesthetics.

The gingival tissues form the soft tissue frame of the dentition and play an important role in dental aesthetics in the maxillary anterior region of the mouth. Alterations to the form and symmetry of the gingivae through developmental, pathologic or iatrogenic factors can significantly alter the appearance and harmony of the natural dentition or prosthetic tooth replacement. This paper describes the techniques available for the management of gingival recession and for surgical lengthening of the clinical crown with particular emphasis on diagnosis and case selection.

Crown Lengthening↗

PubMed1998

Hirayama disease: MR diagnosis.

We report the MR findings in two cases of Hirayama disease, a kind of cervical myelopathy related to flexion movements of the neck. In flexion MR studies, we can see the striking and pathognomonic picture of anterior shifting of posterior dura at the lower cervical spinal canal. In nonflexion studies, we find that asymmetric cord atrophy, especially at the lower cervical cord, though subtle, is highly suggestive of Hirayama disease. When it is seen, a flexion MR study is warranted to prove this diagnosis.

Adolescent↗

PubMed1998

Extent of collateral sprouting of intact nerve fibers in rats depends on the local availability of nerve growth factor.

We investigated the influence of local administration of anti-nerve growth factor (NGF) serum on collateral nerve fiber sprouting caused by chronic constriction injury (CCI) of the sciatic nerve in rats. CCI was induced in adult Sprague-Dawley rats (six per group) by constriction of the sciatic nerve of the right hind limb. Control rats received no further manipulation. In four other groups, rabbit preimmune (control) serum or low (18 ng) or high (1800 ng) doses of anti-NGF serum were injected into the operated or unoperated hind limb each day for 1 month. We used an Evans dye-labeled plasma extravasation technique to visualize the extent of collateral sprouting. Local injection of anti-NGF serum at both high and low doses, but not control serum, significantly reduced the spread of collateral sprouting from the saphenous nerve into the sciatic nerve innervation territory. High-dose anti-NGF serum did not block collateral sprouting when injected into the contralateral (unoperated) hind limb, indicating that the inhibition of sprouting was not caused by a systemic effect. In conclusion, local administration of anti-NGF serum can block sprouting of collateral fibers after nerve injury. Our findings suggest that collateral sprouting is dependent on the local availability of NGF to nearby intact cutaneous nerve fibers.

Animals↗

PubMed1998

Lhermitte-Duclos disease: first report in Taiwan.

We report a case of Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum), an uncommon disorder of uncertain pathogenesis characterized by disarrangement of the normal cerebellar laminar cytoarchitecture. A 40-year-old man was admitted because of vomiting and syncope of a few days' duration, and a 2-month history of intermittent headaches and unsteady gait. A computed tomographic scan of the patient's head showed obstructive hydrocephalus due to displacement of the fourth ventricle by a large, nonenhancing cerebellar mass. The magnetic resonance images of the brain also revealed a space-occupying lesion within the right cerebellum with unusual septation. After surgery, the histologic examination confirmed the diagnosis of Lhermitte-Duclos disease. This is the first report of Lhermitte-Duclos disease in Taiwan.

Adult↗