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Biomedical subjects

J F Chen

Publications and source records attributed to J F Chen.

At least 19 recordsLinked to original sources

Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis.

This study compared the clinical efficacy, safety, and tolerability of daily subcutaneous injections of teriparatide and salmon calcitonin in the treatment of postmenopausal women with established osteoporosis in Taiwan. This 6-month, multicenter, randomized, controlled study enrolled 63 women with established osteoporosis. They were randomized to receive either teriparatide 20 microg or calcitonin 100 IU daily in an open-label fashion. Lumber spine, femoral neck, total hip bone mineral density (BMD), and biochemical markers of bone turnover were measured, and adverse events and tolerability were recorded. The results at 6 months showed that patients using teriparatide had larger mean increases in spinal BMD than those who used calcitonin (4.5% vs. 0.1%), but the BMD changes in these two groups at the femoral neck and the total hip were not significant. There were also larger mean increases in bone markers in the teriparatide group than in the calcitonin group (bone specific alkaline phosphatase 142% vs. 37%; osteocalcin 154% vs. 23%). We conclude that teriparatide has more positive effects on bone formation than salmon calcitonin, as shown by the larger increments of lumbar spine BMD and bone formation markers, and caused only mild adverse events and no significant change in liver, kidney or hematological parameters. Compared with the published global results, teriparatide seems to be equally effective and safe to use in this Asian population.

Aged↗

Adenosine A2A receptors in diffuse dermal fibrosis: pathogenic role in human dermal fibroblasts and in a murine model of scleroderma.

OBJECTIVE: Adenosine regulates inflammation and tissue repair, and adenosine A2A receptors promote wound healing by stimulating collagen matrix production. We therefore examined whether adenosine A2A receptors contribute to the pathogenesis of dermal fibrosis. METHODS: Collagen production by primary human dermal fibroblasts was analyzed by real-time polymerase chain reaction, 14C-proline incorporation, and Sircol assay. Intracellular signaling for dermal collagen production was investigated using inhibitors of MEK-1 and by demonstration of ERK phosphorylation. In vivo effects were studied in a bleomycin-induced dermal fibrosis model using adenosine A2A receptor-deficient wild-type littermate mice, C57BL/6 mice, and mice treated with adenosine A2A receptor antagonist. Morphometric features and levels of hydroxyproline were determined as measures of dermal fibrosis. RESULTS: Adenosine A2A receptor occupancy promoted collagen production by primary human dermal fibroblasts, which was blocked by adenosine A2A, but not A1 or A2B, receptor antagonism. Adenosine A2A receptor ligation stimulated ERK phosphorylation, and A2A receptor-mediated collagen production by dermal fibroblasts was blocked by MEK-1 inhibitors. Adenosine A2A receptor-deficient and A2A receptor antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis. CONCLUSION: These results demonstrate that adenosine A2A receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the treatment and prevention of dermal fibrosis in diseases such as scleroderma.

Animals↗

Adenosine A2A receptors and metabotropic glutamate 5 receptors are co-localized and functionally interact in the hippocampus: a possible key mechanism in the modulation of N-methyl-D-aspartate effects.

Hippocampal metabotropic glutamate 5 receptors (mGlu5Rs) regulate both physiological and pathological responses to glutamate. Because mGlu5R activation enhances NMDA-mediated effects, and given the role played by NMDA receptors in synaptic plasticity and excitotoxicity, modulating mGlu5R may influence both the physiological and the pathological effects elicited by NMDA receptor stimulation. We evaluated whether adenosine A2A receptors (A(2A)Rs) modulated mGlu5R-dependent effects in the hippocampus, as they do in the striatum. Co-application of the A(2A)R agonist CGS 21680 with the mGlu5R agonist (RS)-2-chloro-s-hydroxyphenylglycine(CHPG) synergistically reduced field excitatory postsynaptic potentials in the CA1 area of rat hippocampal slices. Endogenous tone at A(2A)Rs seemed to be required to enable mGlu5R-mediated effects, as the ability of CHPG to potentiate NMDA effects was antagonized by the selective A(2A)R antagonist ZM 241385 in rat hippocampal slices and cultured hippocampal neurons, and abolished in the hippocampus of A(2A)R knockout mice. Evidence for the interaction between A(2A)Rs and mGlu5Rs was further strengthened by demonstrating their co-localization in hippocampal synapses. This is the first evidence showing that hippocampal A(2A)Rs and mGlu5Rs are co-located and act synergistically, and that A(2A)Rs play a permissive role in mGlu5R receptor-mediated potentiation of NMDA effects in the hippocampus.

Adenosine↗

Complications of fixation to the occiput-anatomical and design implications.

Internal fixation provides an increased immediate stability for the craniovertebral junction; however, there is no current consensus on the optimal method of occipitocervical (OC) fusion. In this report, we present 25 cases of craniovertebral instability treated with OC fusion by plates and screws instrumentation. The 25 cases comprised 12 men and 13 women, whose ages ranged 20 to 78 years. The principal aetiologies that lead to the OC instability of the patients in this series included trauma, rheumatoid arthritis, neoplasm and congenital abnormality. The fusion levels ranged from occiput-C3 to occiput-C6. Two mortalities occurred. The other patients showed satisfactory union after a follow-up of eight to 24 months. OC fusion using a plates and screws system is a safe and highly effective method for providing immediate internal stability to the OC junction. The internal occipital anatomy, which cannot be seen at surgery, is important when dealing with this taxing and potentially dangerous aspect of surgery.

Adult↗

Study on the relation between occupational fenvalerate exposure and spermatozoa DNA damage of pesticide factory workers.

AIMS: To determine sperm nuclear DNA integrity and to investigate the relation between fenvalerate (FE) exposure and spermatozoa DNA damage. METHODS: Sperm DNA fragmentation was detected by a modified alkaline single cell gel electrophoresis (Comet) assay and a terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. The olive tail moment (OTM) and percentage tail DNA were measured by the Comet assay, and cell positive percentage was measured by the TUNEL assay for DNA damage evaluation. RESULTS: The DNA integrity of spermatozoa of external and internal control groups were both significantly greater than that of the FE exposed group. The median value of tail DNA percentage in the exposure group was 11.30, which was significantly higher than 5.60 in the internal control group and 5.10 in the external control group. The median value of OTM was 3.80 in the exposure group, significantly higher than 1.50 in the internal control group and 2.00 in the external control group. Mean cell positive was 31.2% in the exposure group, significantly higher than 17.4% in the internal control and 19.6% in the external control groups. Cell positive (%) was significantly correlated with tail DNA percentage and with OTM of whole subjects (n = 63). CONCLUSIONS: Results showed that occupational FE exposure is associated with an increase in sperm DNA damage. A combination of the Comet and TUNEL assays would offer more comprehensive information for a better understanding of sperm DNA damage, and the biological significance of sperm DNA damage in sperm function and male infertility.

Adult↗

[Experimental research of protective and therapeutic effects of zinc and vitamin E on mouse liver radiational damage].

OBJECTIVE: To study the effects of zinc and vitamin E on lipid peroxide (LPO) contents and glutathione peroxidase (GSH-Px) activities in liver homogenates of radiational damage mice. METHODS: Two hundred and forty mice were divided randomly into five groups: normal control group (Group A), 60Co gamma-ray irradiator group (Group B), 60Co + zinc (Zn) group (Group C), 60Co + vitamin E(VE) group (Group D), and 60Co + Zn + VE group (Group E). After irradiated with 60Co gamma-ray 7.5 Gy, the mice were protectively treated with Zn and VE at different times. LPO contents and GSH-Px activities in liver homogenates of the mice were determined. RESULTS: The level of liver LPO was significantly higher (P < 0.01), but the level of liver GSH-Px was significantly lower (P < 0.01) in Group B than those in Group A; the content of liver GSH-Px was markedly higher in Group C and Group D than that in Group B (P < 0.01), while the content of liver LPO was markedly lower in Group D than that in Group B (P < 0.05); the concentration of liver GSH-Px was markedly higher in Group E than that in Group D (P < 0.01). CONCLUSIONS: VE may play an important role in lowering liver LPO contents and raising liver GSH-Px activities in radiational damage mice. vitamin E can cooperate with zinc in raising liver GSH-Px activities, stopping liver cells from lipids peroxidation and keeping integrity of liver cell membrane.

Animals↗

Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease.

Recent epidemiological studies have established an association between the common consumption of coffee or other caffeinated beverages and a reduced risk of developing Parkinson's disease (PD). To explore the possibility that caffeine helps prevent the dopaminergic deficits characteristic of PD, we investigated the effects of caffeine and the adenosine receptor subtypes through which it may act in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin model of PD. Caffeine, at doses comparable to those of typical human exposure, attenuated MPTP-induced loss of striatal dopamine and dopamine transporter binding sites. The effects of caffeine were mimicked by several A(2A) antagonists (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261), 3,7-dimethyl-1-propargylxanthine, and (E)-1,3-diethyl-8 (KW-6002)-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) (KW-6002) and by genetic inactivation of the A(2A) receptor, but not by A(1) receptor blockade with 8-cyclopentyl-1,3-dipropylxanthine, suggesting that caffeine attenuates MPTP toxicity by A(2A) receptor blockade. These data establish a potential neural basis for the inverse association of caffeine with the development of PD, and they enhance the potential of A(2A) antagonists as a novel treatment for this neurodegenerative disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene-deficient mice.

Agonist binding to extracellular A2A adenosine receptors (A2ARs) inhibits the activation of virtually all tested functions of T-cells and can induce apoptosis in thymocytes. The evaluation of levels of expression of these immunosuppressive receptors is expected to clarify whether the absence of spare A2ARs (no 'receptor reserve') might be one of the mechanisms of attenuation of the effects of extracellular adenosine on T-cells. A2A transcript is found in T-cells and functional receptors can be demonstrated, but the density of receptor on T-cells is too low to be detected by radioligand binding. Studies of direct radioligand binding to murine brain with the selective A2AR agonist [3H]CGS21680 (2-(4-[(2-carboxyethyl)-phenyl]ethylamino)-5'-N-ethylcarboxamidoadenosine) established that striata levels of A2AR are virtually absent from A2A knock-out mice. Mice that are heterozygous (A2AR+/-) for the A2AR express significantly decreased levels of A2AR. To test for the presence of spare receptors in T-cells we took advantage of this gene dose effect and examined whether the decrease in the number of receptors in thymocytes from A2AR+/- mice was proportionately reflected in a decrease in the functional cAMP response of T-cells to adenosine. cAMP accumulation and apoptosis induced by adenosine and by A2AR agonist are of a lower magnitude in T-cells from A2AR+/- heterozygous mice than in T-cells from A2AR+/+ littermate control mice. These results indicate that there is no A2AR reserve in murine T-cells. Strongly decreased adenosine-triggered cAMP increases were detected in thymocytes from A2AR-/- mice, suggesting that A2B adenosine receptors cannot fully compensate for the loss of A2ARs in murine T-cells. We conclude that the number of A2ARs is the limiting factor in determining the maximal cAMP response of T-lymphocytes to extracellular adenosine, thereby minimizing the immunosuppressive effects of extracellular adenosine.

Animals↗

The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice.

The A(2A)R is largely coexpressed with D(2)Rs and enkephalin mRNA in the striatum where it modulates dopaminergic activity. Activation of the A(2A)R antagonizes D(2)R-mediated behavioral and neurochemical effects in the basal ganglia through a mechanism that may involve direct A(2A)R-D(2)R interaction. However, whether the D(2)R is required for the A(2A)R to exert its neural function is an open question. In this study, we examined the role of D(2)Rs in A(2A)R-induced behavioral and cellular responses, by using genetic knockout (KO) models (mice deficient in A(2A)Rs or D(2)Rs or both). Behavioral analysis shows that the A(2A)R agonist 2-4-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine reduced spontaneous as well as amphetamine-induced locomotion in both D(2) KO and wild-type mice. Conversely, the nonselective adenosine antagonist caffeine and the A(2A)R antagonist 8-(3-chlorostyryl)caffeine produced motor stimulation in mice lacking the D(2)R, although the stimulation was significantly attenuated. At the cellular level, A(2A)R inactivation counteracted the increase in enkephalin expression in striatopallidal neurons caused by D(2)R deficiency. Consistent with the D(2) KO phenotype, A(2A)R inactivation partially reversed both acute D(2)R antagonist (haloperidol)-induced catalepsy and chronic haloperidol-induced enkephalin mRNA expression. Together, these results demonstrate that A(2A)Rs elicit behavioral and cellular responses despite either the genetic deficiency or pharmacological blockade of D(2)Rs. Thus, A(2A)R-mediated neural functions are partially independent of D(2)Rs. Moreover, endogenous adenosine acting at striatal A(2A)Rs may be most accurately viewed as a facilitative modulator of striatal neuronal activity rather than simply as an inhibitory modulator of D(2)R neurotransmission.

Adenosine↗

Effect of alanine-293 replacement on the activity, ATP binding, and editing of Escherichia coli leucyl-tRNA synthetase.

Leucyl-tRNA synthetase (LeuRS) is a class I aminoacyl-tRNA synthetase that catalyzes leucylation of tRNA(Leu). Several mutants in the CP1 domain of Escherichia coli LeuRS were obtained by introduction of restriction endonuclease sites into its gene, leuS. Of these mutants, only LeuRS-A293F had decreased activity (46%) compared to the native enzyme. To investigate the effect of A293 on enzyme function, A293 was mutated to Y, G, I, R, or D. The mutants were impaired in activity and editing function to varying extents. The decrease in K(m) values for three substrates showed that the binding of ATP to these mutants became much stronger. The inhibition of ATP binding to most of the mutants was also stronger. In particular, LeuRS-A293D had the lowest activity, the strongest ATP binding, and the most impaired editing function. A red shift of the fluorescence emission maximum of LeuRS-A293D indicated a less hydrophobic chromophore environment and a relatively more flexible dynamic conformation. The change in T(m) of LeuRS-A293D was higher than that of all other substitutions. Evidence from sequence alignment and crystal structure of LeuRS from Thermus thermophilus shows that A293 was conserved as R (K) or A and is located at a small helix in the editing domain of the enzyme facing the active site. Hence, any amino acid substitution of A293 may affect the stability of the helix, which may lead to impaired editing function and aminoacylation activity and may be indirectly involved in ATP binding.

Acylation↗

In vivo hemodynamic performance of the Cleveland Clinic CorAide blood pump in calves.

BACKGROUND: The Cleveland Clinic CorAide left ventricular assist system is based on a small implantable continuous-flow centrifugal blood pump with a completely suspended rotating assembly designed for long-term circulatory support (5 to 10 years). METHODS: Between June 1999 and August 2000, the CorAide blood pump was implanted in 10 calves for 1 month and in 3 calves for 3 months. RESULTS: The mean pump flow and arterial pressure were 6.1 +/- 1.1 L/min and 97 +/- 5 mm Hg, respectively. The mean plasma free-hemoglobin level after postoperative day 3 was 2.0 +/- 1.8 mg/dL. Renal and hepatic function remained normal in all cases. There was no incidence of mechanical failure, hemolysis, bleeding, or systemic organ dysfunction in any of the cases. Significant findings at autopsy were limited to two cases of renal infarction, one of which was associated with an outflow graft infection. CONCLUSIONS: The CorAide blood pump is easily implanted, reliable, nonhemolytic, and nonthrombogenic, positioning it as a leading third-generation, continuous-flow left ventricular assist system with a completely suspended rotor.

Animals↗

Evaluation of bone mineral density by quantitative ultrasound of bone in 16,862 subjects during routine health examination.

Caucasians and Asians are among those with the highest risk for involutional osteoporosis. To obtain accurate data about the prevalence of osteoporosis or osteopenia in different age groups, a large epidemiological study is necessary. Quantitative ultrasound (QUS) of bone is a promising technique in assessing bone microarchitecture in addition to bone mass. This study had two aims. The first was to establish bone mineral density (BMD) using QUS in subjects with no obvious disease undergoing routine health examination. The second was to determine risk factors for osteoporosis in Taiwan in order that better prevention and treatment measures may be provided for these patients. A prospective study of the risk factors for fracture was conducted in the health examination division of Chang Gung Medical Center in Linkou, Taiwan, from January 1996 to December 1997. Broadband ultrasound attenuation of the right heel was measured with an achilles bone densitometer (Lunar, Nauheim, Germany). A total of 16,862 subjects were examined, including 9,314 women (mean age 51.5+/-11.7 years) and 7,548 men (mean age 51.1+/-12.1 years). The incidence of osteoporosis in all subjects increased from 1.13% in the 21--30-year-old age group to 54.55% in those over 80 years of age. 12.02% of the subjects had osteoporosis and 34.45% had osteopenia. From multivariate analysis, bone density evaluated by QUS showed a relationship with age, gender, body mass index, waist/hip ratio, smoking and frequency of exercise. In conclusion, BMD evaluated by QUS is not found to be higher in Taiwan than elsewhere. The role of QUS in predicting fractures in Taiwan requires further investigation.

Adolescent↗

[Development of Triticum aestivum-Haynaldia villosa 6VS ditelosomic substitution line via phlb mutant].

Chinese Spring phlb mutant (C S phlbphlb) was crossed to Triticum aestivum-Haynaldia villosa 6V (6A) alien substitution line and F1 back was crossed with C. S phlbphlb. One LV 02 with varied H. villosa 6V chromosome and one LV 02-01 with 40 T. aestivum chromosome, one H. villosa 6V and 6VS chromosome were screened in BC1F1 and BC1F2 respectively by C-banding and the fluorescence in situ hybridization (FISH). In segregated generation of LV 02-01, eight T. aestivum-H. villosa 6VS ditelosomic substitution lines were screened by FISH and C-banding.

Chromosome Banding↗

Recurrence of pneumococcal meningitis due to primary spontaneous cerebrospinal fluid fistulas.

The authors report a case of pneumococcal meningitis which recurred 3 times in a Taiwanese boy due to spontaneous cerebrospinal fluid (CSF) fistulas. The first time occurred at the age of 2 years, and the second episode presented as meningoencephalomyelitis at the age of 6 years 10 months. Studies including serum levels of immunoglobulin and complements, brain magnetic resonance imaging, and coronal cranial computed tomography (CT) were negative for a specific etiology. The third episode of meningitis developed 2 months after the second episode. Repeated immunological studies and high-resolution CT of paranasal sinuses and temporal bones were negative. Technetium-99m diethylenetriamine pentaacetic acid (Tc-99m-DTPA) radionuclide cisternography revealed abnormal retention of radioactivity over the right mastoid area. Neurosurgery was undertaken to seal the dural tear and pack the petrosal fissure. Two years after surgery, he has had no further CSF leak age or meningitis. Tracing back the history, there was no head injury, cranial surgery, brain tumor, or hydrocephalus, which might have created CSF fistulas. Primary spontaneous CSF fistulas constitute the most reasonable diagnosis. In cases of recurrent bacterial meningitis, underlying anatomic defects should be carefully evaluated if there is no immune defect.

Cerebrospinal Fluid Rhinorrhea↗

[Experimental study on the pathogenesis of Entamoeba gingivalis].

OBJECTIVE: To study the pathogenesis of Entamoeba gingivalis (E. g.) and its relation to periodontal diseases. METHODS: Rats were treated with immuno-inhibitor for one week and the neck of incisor teeth of the rats was bound with steel wire. They were randomly divided into three groups: the first group was infected by E. g. in the periodontal tissue, the second group was infected by symbiotic bacteria (s. b.), and the third group was given physiological saline as control. Observation on the periodontal inflammation was made for each group of rats, and the purulent secretion from periodontal abscess was examined for living pathogens. RESULTS: The incidence of periodontal diseases in rats infected by E. g. was higher than that of symbiotic bacteria group and that of control (P < 0.05), the incidence of periodontal diseases in rats infected by s. b. was higher than that of control group (P < 0.05). Living pathogens were found in the abscess liquid. CONCLUSION: E. g. is an opportunistic pathogen, which, together with synergistic symbiotic bacteria, can cause periodontal diseases in hosts with low immunity.

Animals↗

[Studies on ultrastructure and histochemistry of Trichomonas vaginalis adhering to vaginal mucosa of rats].

OBJECTIVE: To study interaction between Trichomonas vaginalis and epithelium of genital tract of host as well as the pathogenesis of T. vaginalis. METHODS: Immunohistochemical technique was used to observe the adhering process of T. vaginalis to vaginal mucosa in rats by transmission and scanning microscopy. RESULTS: T. vaginalis were shown to be PAS positive and clusters of T. vaginalis were found to adhere to columnar epithelium rich in mucopolysaccharide on the surface of vaginal mucosa as viewed in sections of the middle and upper parts of the orgen. T. vaginalis was positive for cathepsin. And the membrane of epithelial cells was often damaged by the released hydrolase. The parasite was also positive for actin; the microfilament bundles were arranged in reticular form in ameboid T. vaginalis. The latter would penetrate between epithelial cells, and its filiform pseudopodia would invade the interspace of microvilli of the epithelium, to encircle and gradually phagocytize microvilli. Digitiform pseudopodia would insert between epithelial cells and encircle part of them. A few T. vaginalis were found to adhere to the keratinized epithelium between mucosal folds as shown in the sections of the lower part of vagina. CONCLUSION: T. vaginalis is inclined to parasitise vaginal fornix because the superficial epithelial cells there are rich in mucinogen granules and abundant microvilli exist. After adhering, T. vaginalis releases hydrolase to digest and phagocytize epithelium which may directly damage the epithelium of the genital canal. Moreover, T. vaginalis would take in mucopolysaccharide to affect the normal clearance process of vagina, resulting in inflammation of parasitized tissue. The cytoskeleton, cell coat, polymorphism of pseudopodia and lysosome of T. vaginalis play an important role in the courses of movement, adhesion, encirclement, phagocytosis and digestion.

Actins↗