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Biomedical subjects

H J Chen

Publications and source records attributed to H J Chen.

At least 55 records · Page 3Linked to original sources

Ca2+-dependent and Ca2+-independent excretion modes of salicylic acid in tobacco cell suspension culture.

14C-salicylic acid (SA) was used to monitor SA metabolism and its regulation in tobacco cell suspension culture. Two SA concentrations (20 microM and 200 microM) were used for comparison. SA was quickly taken up in both treatments, and the 200 microM-treated cells absorbed approximately 15 times that of 20 microM-treated cells within 5 min. More than 85% and 50% of the absorbed SA were excreted in free form to the culture medium within 5 h from cells treated with 200 microM and 20 microM SA, respectively. SA excretion was significantly inhibited by EGTA and the inhibition could be reversed by the addition of exogenous Ca2+ to the culture medium in the 200 microM SA treatment. However, EGTA had little or no effect on SA excretion in the 20 microM SA treatment. The data suggest that tobacco suspension-cultured cells may contain both Ca2+-dependent and Ca2+-independent pathways for SA excretion. Reduced glutathione (an active oxygen species scavenger), staurosporine (a protein kinase inhibitor), and cycloheximide (an inhibitor of de novo protein synthesis) also blocked intracellular SA excretion to the culture medium in the 200 microM but not in the 20 microM SA treatment. These data support the existence of alternative SA excretion pathways in tobacco suspension-cultured cells. Tobacco cells may use both Ca2+-dependent and Ca2+-independent excretion pathways to cope with different intracellular SA status, and the pathway influenced by EGTA, reduced glutathione, staurosporine, and cycloheximide is activated by SA at 200 microM, but not at 20 microM.

Autoradiography↗

Differential telomerase expression and telomere length in primary intracranial tumors.

BACKGROUND: Telomerase activity and telomere length have been shown to be involved in controlling cell proliferation and regulating cell senescence. The authors examined telomerase activity and telomere length in intracranial tumors to determine the clinicopathological behavior of primary intracranial tumors with respect to telomerase expression and alteration of telomere length. METHODS: Telomerase activity was examined in 139 brain tumor samples. Telomere length was examined in 138 of the 139 samples. These tumors included 61 meningiomas, 27 schwannomas, 19 high-grade neuroepithelial tumors, and 32 low-grade neuroepithelial tumors. Telomerase activity was measured with a telomerase polymerase chain reaction, enzyme-linked immunosolvent assay kit. Telomere length was examined by Southern blot analysis for the terminal restriction fragment length. RESULTS: Telomerase activity was detected in 39.2% (20/51) of the neuroepithelial tumors. Detection rates were 47.4% (9/19) for anaplastic astrocytomas and glioblastomas and 34.4% (11/32) for low-grade neuroepithelial tumors. However, detectable telomerase activity was found in 30.8% (4/13) of atypical or malignant meningiomas, but was not detected in any schwannomas. There was a highly significant difference in the telomerase detection rate in neuroepithelial or non-neuroepithelial tumors (p = 0.001). Telomere elongation was found in 11.7% (7/60) of all meningiomas, 46.1% (6/13) of atypical or malignant meningiomas, and 14.8% (4/27) of schwannomas. Elongation of telomere length was detected in 12.6% (11/87) of the cases and 23.5% (12/51) in neuroepithelial tumors. This difference was also significant (p < 0.05). Telomere length was reduced in the majority, (75%, 3/4) of malignant or atypical meningiomas with detectable telomerase activity, but only 45% (9/20) of the neuroepithelial tumors. CONCLUSION: These results indicate that telomerase activation may be a critical step in the pathogenesis of intracranial tumors. Telomere length elongation also indicates a high potential for malignant behavior in these tumors.

Adolescent↗

Patterns of palmar skin temperature alterations during transthoracic endoscopic T2 sympathectomy for palmar hyperhidrosis.

Transthoracic endoscopic T2 sympathectomy has been widely applied to the treatment of a variety of sympathetically mediated disorders. Palmar hyperhidrosis is probably the most common indication for thoracic sympathectomy, especially in certain subtropical areas. Which sympathetic ganglion is to be ablated and how extensive such ablation is enough to eliminate palm sweating are two important issues. Intraoperative monitoring of palmar skin temperature (PST) is the most frequently used method for assessing the accuracy as well as adequacy of ablation of the target sympathetic ganglia. With continuous monitoring of bilateral PST during the operative course of T2 sympathectomy, it was possible to depict the alterations of bilateral PST in response to specific surgical procedures in a real-time manner. For each case, a PST graph was obtained, which represented the graphical expression of intraoperatively recorded bilateral PST data plotted against time. The PST graphs of 93 consecutive cases were analysed. Three types of PST graphs existed, reflecting different responses of bilateral PST to different surgical procedures during the operation. In Type I PST graph pattern, found in 58 cases, skin incision and intercostal muscle dissection caused dramatic bilateral PST drop; and unilateral T2 sympathectomy induced synchronous bilateral PST elevation. Twenty-four cases demonstrated Type II PST graph pattern, in which unilateral T2 sympathectomy caused only ipsilateral PST elevation, although the PST-depressing effect of skin incision and muscle dissection was as significant as in Type I graph pattern. In the 11 cases who showed Type III PST graph pattern, neither skin incision nor T2 sympathectomy induced any apparent changes of PST on either side, giving rise to two rather flat PST curves on the PST graphs. These findings implicate that reciprocal interactions between bilateral sympathetic activities exist in the majority of cases, and that crossover sympathetic modulation may play a role in the neural control of the sudomotor and vasomotor activities of the palms. This study also provides information regarding how PST would possibly change following specific surgical procedures during transthoracic endoscopic T2 sympathectomy, which may be of importance to those who use intraoperative PST monitoring as a guide in determining whether or not the correct sympathetic ganglia are ablated for adequate sympathetic denervation of the palms.

Adolescent↗

Implication of telomerase activity and alternations of telomere length in the histologic characteristics of intracranial meningiomas.

BACKGROUND: Telomerase activity and telomere length have been shown to be involved in the control of cell proliferation and regulation of cell senescence. The expression of telomerase activity may endow cells with the capacity of unlimited proliferation and immortality. The authors examined the telomerase activity and telomere length of intracranial meningiomas to determine the relation between the results and the clinicopathologic behavior of these tumors. METHODS: Sixty-two specimens of meningiomas including 13 atypical and malignant tumors were used in this study. Telomerase activity was measured with polymerase chain reaction and enzyme-linked immunosolvent assay. Telomere length was measured by detecting the terminal restriction fragments using Southern blots. RESULTS: Detectable telomerase activity was found in 4 of 13 (30.8%) malignant or atypical meningiomas and only 1 in 49 benign meningiomas (P = 0.006). Elongated telomere length was measured in 6 of 13 (46.1%) patients with malignant or atypical meningiomas and only 1 of 48 (2.1%) in those with benign tumors (P = 0.0002). Three of 4 (75%) of malignant or atypical meningiomas with detectable telomerase activity revealed shortened telomere length, and all tumors with elongated telomere length displayed undetectable telomerase activity. The percentage of malignant or atypical meningiomas with detectable telomerase activity or elongated telomere were significantly higher (76.9%) than that of benign tumors (4.0%). The proliferative index was calculated as the percentage of tumor cell nuclei immunoreactive for Ki-67 to total tumor nuclei. The mean values of proliferative index in benign, atypical, and malignant meningiomas were 1.2, 11.0, and 30.0, respectively. CONCLUSIONS: The results indicate that telomerase activation may be a critical step in the pathogenesis of malignant or atypical meningioma. Elongation of the telomere length also implicates the high potential for malignant behavior in these tumors.

Adult↗

Elevated levels of plasma C-reactive protein are associated with decreased graft survival in cardiac transplant recipients.

BACKGROUND: Inflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival. METHODS AND RESULTS: We studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0+/-2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure (P:=0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection (P:=0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure (P:=0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level. CONCLUSIONS: These findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.

Biomarkers↗

Delayed apnea in patients with mid- to lower cervical spinal cord injury.

STUDY DESIGN: A retrospective study of 36 patients with mid- to lower cervical spinal cord injury (CSCI) divided into two groups based on whether delayed apnea developed. OBJECTIVES: To determine nonpulmonary risk factors associated with the development of delayed apnea in mid- to lower cervical spinal cord injury. SUMMARY OF BACKGROUND DATA: Patients with mid- to lower cervical spinal cord injury are generally at lower risk of developing respiratory failure than those with high cervical spinal cord injury. Respiratory failure manifesting as sudden apnea may occur days or even weeks after injury without any pulmonary complications in such patients. METHODS: An index group of eight patients with complete mid- to lower cervical spinal cord injury in whom delayed catastrophic apnea occurred were reviewed. Another group of 28 patients with cervical spinal cord injury of identical magnitude and presentation but without respiratory failure served as the control group. Six parameters presumed to be related to the delayed apnea were analyzed. RESULTS: The extent of cord lesions was significantly different, being diffuse in most of the index patients, but focal in the majority of the control patients (P<0.001). Involvement of the C4 segment of cord appeared to be more frequent in the index group; however, the difference was not statistically significant (P = 0.091). The incidence of transient bradycardia (P<0.01) and dyspnea (P<0.001) in the index group was significantly higher than in the control group. Paralytic ileus was a much rarer event and found to be unrelated to the occurrence of apnea. In five of the eight index patients, the apnea occurred during sleep. Six of the eight index patients died of it. CONCLUSIONS: Delayed but devastating apnea may develop in patients with mid- to lower cervical cervical spinal cord injury, even when they are clinically stable and free from any pulmonary complications. The presence of diffuse, extensive cord lesions, respiratory distress, or bradycardia with or without associated hypotension, however transient and self-limited, should be regarded as warning signs. Sleep was found to be a risky period of time.

Adult↗

Degradation of DNA topoisomerase I by a novel trypsin-like serine protease in proliferating human T lymphocytes.

DNA topoisomerase I (Topo I) contributes to various important biological functions, and its activity is therefore likely regulated in response to different physiological conditions. Increases in both the synthesis and degradation of Topo I were previously shown to accompany phytohemagglutinin stimulation of proliferation in human peripheral T lymphocytes. The mechanism of this degradation of Topo I has now been investigated with both in vivo and in vitro assays. The activity of a nuclear protease that specifically degrades Topo I was induced in proliferating T lymphocytes. The full-length Topo I protein (100 kDa) was sequentially degraded to 97- and 82-kDa fragments both in vivo and in vitro. The initial site of proteolytic cleavage was mapped to the NH(2)-terminal region of the enzyme. The degradation of Topo I in vitro was inhibited by aprotinin or soybean trypsin inhibitor, suggesting that the enzyme responsible is a trypsin-like serine protease. Furthermore, Topo I degradation by this protease was Mg(2+)-dependent. The Topo I-specific protease activity induced during T lymphocytes proliferation was not detected in Jurkat (human T cell leukemia) cells and various other tested human cancer cell lines, possibly explaining why the abundance of Topo I is increased in tumor cells.

Acetylcysteine↗

Transcriptional repression of p21((Waf1/Cip1/Sdi1)) gene by c-jun through Sp1 site.

Previously, we found that c-jun represses the tumor suppressor p21((Waf1/Cip1/Sdi1)) (p21) gene expression. In this study, we further investigated the mechanism of the inhibitory effect of c-jun on p21. After analysis of a series of deletion and point mutants of p21 promoter, we found that Sp1-3 site (-77 and -83) relative to the transcription start site played an important role for c-jun-repressing-responsive element in the p21 promoter. Both Sp1 and Sp3 transcription factors were the key factors for this event. However, the data from electrophoretic mobility shift assay indicated that c-jun did not change the Sp1 DNA-binding affinity, suggesting that additional factors may be involved in the repression of p21 by c-jun. Furthermore, c-jun could inhibit butyrate-inducing p21 gene expression through Sp1, indicating at least one common pathway whereby p21 expression is affected by c-jun and butyrate in opposing actions. Moreover, the hyperphosphorylated retinoblastoma protein (Rb) increased in c-jun expressing cells, indicating that phosphorylated Rb may play a role in regulating Sp1 to repress p21 expression. This is the first demonstration of how housekeeping factors and oncogene product counteract the function of tumor suppressor genes to control cell cycle progression.

Binding Sites↗

Total synthesis and antifungal evaluation of cyclic aminohexapeptides.

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported.

Acute Disease↗

Angiogenically active vascular endothelial growth factor is over-expressed in malignant human and rat prostate carcinoma cells.

Vascular endothelial growth factor (VEGF) is one of the most potent factors for stimulating angiogenesis, an essential process required for expansion of primary tumour and dissemination of malignant cells. To investigate the possible role of VEGF in facilitating metastasis of prostate cancer via stimulating angiogenesis, we have used Northern and slot blotting, reverse transcription polymerase chain reaction, nucleotide sequence analysis and enzyme-linked immunosorbent assay to compare the VEGF expression in series of human and rat cell lines with either benign or malignant characteristics. We have also employed the chick chorioallantoic membrane (CAM) assay to measure the angiogenic activity of the VEGF derived from both benign and malignant cells. The level of VEGF mRNA expressed in the seven malignant human and rat cell lines is 3.5- to 10-fold higher than that expressed in the benign cell lines. The three metastatic variants, generated by transfection of a benign cell line with DNA extracted from prostate carcinoma cells, expressed 2.5 to 5 times more VEGF mRNA than their parental benign cells. While VEGF 121 and 165 were predominantly expressed by both the benign and malignant cells, the transcript representing VEGF 189 isoform was only detected in the malignant cells. At protein level, three human malignant cell lines produced more VEGF (2.7-7.9 ng ml(-1)) than the benign cell line (1.3 ng ml(-1)). CAM assay detected a VEGF-dependent angiogenic activity in the medium from malignant cells, but only a relatively weak VEGF-independent activity in the medium from benign cells. These results demonstrated that malignant cells did over-express VEGF and only the VEGF derived from malignant cells was angiogenically active. Thus, we suggest that the VEGF produced by malignant cells might play an important role in facilitating metastasis of prostatic cancer.

Allantois↗

Amniotic membrane transplantation for severe neurotrophic corneal ulcers.

AIMS: To evaluate whether amniotic membrane transplantation can be an effective alternative treatment for neurotrophic corneal ulcers. METHODS: Amniotic membrane transplantation was performed in 16 eyes of 15 patients with neurotrophic corneal ulcers and vision equal to or worse than 20/200. The neurotrophic state was developed following keratoplasty (four eyes), herpes zoster ophthalmicus (four eyes), diabetes mellitus (four eyes), radiation (two eyes), removal of acoustic neuroma with neuroparalysis (one eye), and herpes simplex keratitis (one eye). RESULTS: During a mean follow up period of 18.8 (SD 13.0) months, one to three layers of amniotic membrane with or without additional membrane as a patch were used for 17 procedures in 16 eyes for persistent neurotrophic corneal ulcers. All but four (76.4%) instances of amniotic membrane transplantation achieved rapid epithelialisation in 16.6 (9.0) days. Of the four eyes showing delayed healing, three eyes healed by tarsorrhaphy, and the remaining one eye with corneal perforation required penetrating keratoplasty and tarsorrhaphy. Two eyes gained vision better than 20/200. The healed corneal surface was accompanied by reduced inflammation. CONCLUSION: Amniotic membrane transplantation can be considered an effective alternative for treating severe neurotrophic corneal ulcers.

Adult↗

Changes of bilateral palmar skin temperature in transthoracic endoscopic T-2 sympathectomy.

OBJECT: Transthoracic endoscopic T-2 sympathectomy is currently the treatment of choice for palmar hyperhidrosis (PH). Intraoperative monitoring of palmar skin temperature (PST) is often used to assess the adequacy of sympathetic ablation. The aim of this study was to investigate the time course of PST changes during the operation and to determine factors involved in the sympathetic modulation of the palmar skin blood flow. METHODS: Eighty-one patients with PH underwent bilateral transthoracic endoscopic sympathectomy of T-2 in which continuous intraoperative PST monitoring was used. Palmar skin temperature data, recorded every 30 seconds throughout the operation, were plotted against time, and a graph of two PST curves was obtained in each case. A multiphasic curve pattern of great similarity was observed in nearly 70% of cases. Specific PST readings at different operative stages were collected and averaged for all cases. The trend of PST changes in response to different procedures during the operation was analyzed. It was found that unilateral procedures caused simultaneous bilateral PST alterations. In almost all cases, bilateral PST was dramatically lowered when unilateral skin incision and intercostal muscle dissection were performed. The temperature remained low until the T-2 sympathectomy was finished on one side. In addition, unilateral T-2 sympathectomy induced synchronous elevation of bilateral PST. However, the ipsilateral response was significantly stronger than that on the contralateral side. CONCLUSIONS: Although intraoperative monitoring of PST is a reliable guide for surgeons performing endoscopic transthoracic sympathectomy, it is important to realize that PST fluctuates at different stages during the operation and that surgical procedures themselves can significantly influence PST readings. The PST data recorded at specific time points, therefore, can be misleading in terms of accuracy and the completeness of ablation of the target sympathetic ganglia, especially when the sympathetic trunk or ganglia are anatomically aberrant.

Adolescent↗

Ptosis surgery on chronic myasthenia gravis.

We report three cases of long-standing, early onset myasthenia gravis. The eyes of all three patients eventually became disabled, and the patients were almost unable to move their eyes in any direction. We termed this condition as "frozen eyes" appearance. We discuss the unique clinical condition and follow the electromyographic and neuro-ophthalmological characteristics. The patients all suffered from ptosis, mild to moderate exotropia, and facial and oropharyngeal weakness. All of the patients responded to the neostigmine test positively at the early stage. Two of them were seropositive. The results of electromyography for two of these three cases were abnormal. The average duration of follow-up was 5 years. The treatments included conventional recession and resection procedures with adjustable sutures for strabismus and frontalis suspension for blepharoptosis. The patients achieved stable satisfactory results in over one-and-a-half years of postoperative follow up.

Adult↗

Scanning laser polarimetry in evaluation of retinal nerve fiber layer thickness for normal Taiwanese.

Scanning laser polarimetry has been used recently for the measurement of retinal nerve fiber layer (RNFL) thickness, taking advantage of the birefrigence of the RNFL. We observe the RNFL with the instrument and try to find out a set of normal basic values of the RNFL thickness for clinical comparison. One hundred normal volunteers of different age groups were recruited for this study. There are 44 males and 56 females with a mean (1SD) age of 36.17(14.77) years. Three consecutive 15-degree polarimetric maps were acquired for each subject. RNFL thickness measurements were obtained at 1.75 disc diameters ring from the optic nerve. Four 90-degree quadrants were identified. As a result, the average of RNFL thickness is 90.69 (20.20) microns in the superior quadrant, 80.45 (17.4) microns in the inferior quadrant, 59.28 (15.37) microns in the nasal quadrant, and 48.98 (15.72) microns in the temporal quadrant with a mean thickness value of 69.86 (13.97) microns. Superior and inferior quadrants showed a comparatively thicker nerve fiber layer than nasal and temporal quadrants. The temporal quadrant was always the lowest. The axial length does not affect the RNFL thickness and no significant difference between males and females exists. However, an obvious inverse linear correlation between age and the RNFL thickness in all quadrants is found. The average RNFL thickness decreased with age by 0.26 micron per year. (R2 = 0.081, p-value = 0.004). When compared with the normal range, age-match would be necessary.

Adolescent↗

Urinary uric acid/creatinine ratio as an additional marker of perinatal asphyxia.

PURPOSE: To study the validity of urinary uric acid (UA) as a marker of perinatal asphyxia in term and premature infants. METHODS: The urinary ratio of UA to creatinine (Cr) was obtained within 24 hours after birth in four groups of infants: 17 term infants and 18 premature infants with perinatal asphyxia, and 22 healthy term infants and 20 premature infants without perinatal asphyxia. Perinatal asphyxia was defined as an Apgar score of 3 or less at 1 minute or 5 or less at 5 minutes, and/or a first blood gas pH of less than 7.25 and a base deficit of at least 12 mmol/L. RESULTS: The urinary ratio of UA to Cr was significantly higher in term infants with perinatal asphyxia than in term infants without asphyxia (1.53 +/- 0.71 vs 0.73 +/- 0.45; p < 0.005). The same result was found between premature infants with and without perinatal asphyxia (3.89 +/- 1.84 vs 2.45 +/- 0.88; p < 0.01). The urinary ratio of UA to Cr in premature infants was significantly higher than in term infants. When the urinary ratio of UA to Cr was greater than 0.95, perinatal asphyxia was identified with a sensitivity of 80% and a specificity of 71% in term infants. In premature infants, a cut-off value of UA/Cr for perinatal asphyxia of 2.9 had a sensitivity of 71% and a specificity of 70%. CONCLUSIONS: The results of this study indicate that the urinary ratio of UA to Cr may be used as an additional marker of perinatal asphyxia in term and premature infants. In comparison with other markers such as xanthine, hypoxanthine, and ascorbic acid, it is a simple, quick, and inexpensive way to detect hypoxic episodes in a neonatal intensive care unit within 24 hours after birth.

Asphyxia Neonatorum↗

Mice deficient in hepsin, a serine protease, exhibit normal embryogenesis and unchanged hepatocyte regeneration ability.

Hepsin, a liver-enriched novel serine protease, has been implicated in participating with normal cell growth, embryogenesis, and blood coagulation pathway. To study its function in vivo, we have disrupted the mouse hepsin gene by homologous recombination. Targeted disruption of the hepsin gene and ablation of hepsin message were demonstrated by Southern blotting, Northern blotting and RT-PCR analysis. Homozygous hepsin -/- mice were viable, fertile, and exhibited no gross abnormalities, as judged by the size, weight and blood coagulation (PT) assays. However, the serum concentration of the bone form of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase of the hepsin -/- mice was mildly elevated, in spite of no obvious pathological change of hepatocytes. To examine whether hepsin is involved in controlling cell growth in adult tissues, 70% hepatectomy was applied to the hepsin -/- mice. Liver regeneration proceeded normally in the hepsin -/- mice as judged by the liver mass restoration rate. These results suggest that loss of hepsin function causes no effect in cell growth and embryogenesis in vivo, which is in contradiction to the studies using in vitro cell culturing system. Moreover, gross mass regeneration of liver after damage proceeds normally in the absence of functional hepsin.

Animals↗