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Biomedical subjects

T C Chen

Publications and source records attributed to T C Chen.

At least 37 records · Page 2Linked to original sources

25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue.

Vitamin D affects calcium metabolism and prevents proliferation of colon cells in vitro. In human beings the main circulating form of vitamin D is 25-hydroxyvitamin D; to regulate calcium homoeostasis, this form must be converted to 1alpha, 25-dihydroxyvitamin D by 1alpha-hydroxylation in the kidney with 25-hydroxyvitamin D-1alpha-hydroxylase. Cultured transformed colon cancer cells can convert 25-hydroxyvitamin D(3) to 1alpha,25-dihydroxyvitamin D(3). We identified messenger RNA (mRNA) for 25-hydroxyvitamin D-1alpha-hydroxylase in normal colon tissue and in malignant and adjacent normal colon tissue. These findings support the notion that vitamin D might have a role in cell growth regulation and cancer protection, and might be the explanation for why the risk of dying from colorectal cancer is highest in areas with the least amount of sunlight.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Genome-wide hypomethylation in hepatocellular carcinogenesis.

Aberrant genome-wide hypomethylation has been thought to be related to tumorigenesis. However, its mechanism and implications in hepatocellular carcinogenesis remain to be elucidated. Samples of hepatoma (hepatocellular carcinoma, HCC) and paired non-HCC liver tissues were obtained from 17 HCC patients. Normal liver tissues obtained from three individuals were used as controls. Compared with the paired non-HCC liver tissues, genome-wide 5-methylcytosine content in HCC was reduced in all of the tested HCC samples (P < 0.001). Conversely, genome-wide 5-methylcytosine content did not significantly differ among normal, noncirrhotic, and cirrhotic liver tissues. Moreover, the degree of reduced DNA methylation was related to late histopathological HCC grade (P = 0.005) and large tumor size (P = 0.079). Compared with the paired non-HCC liver tissues, expression of DNA methyltransferases DNMT-1, DNMT-3A, and DNMT-3B and the DNA methyltransferase-like gene, DNMT-2, was up-regulated in 53, 41, 59, and 47% of the HCC samples, respectively. Surprisingly, small amounts of LINE-1 retrotransposon transcripts were detected in HCC and non-HCC as well as normal liver tissues, and the expression levels were not significantly different in HCC compared with the paired non-HCC or normal liver tissues. Of interest, the 3' ends of these LINE-1 transcripts were truncated. Our findings suggest that genome-wide hypomethylation in HCC is a continuing process that persists throughout the lifetime of the tumor cells rather than a historical event occurring in precancer stages or in cell origins for HCC. Up-regulation of DNA methyltransferases might simply be a result of increased cell proliferation in cancer. In addition, our results did not support the hypothesis of activation of transposable elements in HCC via genome-wide hypomethylation.

5-Methylcytosine↗

Angiomyolipoma of the liver.

BACKGROUND AND OBJECTIVES: Angiomyolipoma is a rare benign tumor that occurs in the liver and other organs. We provide data on eight cases of hepatic angiomyolipoma, regarding clinical presentations, diagnoses, management, and prognosis. METHODS: A retrospective review of medical records of the eight patients with hepatic angiomyolipoma treated at the Chang Gung Memorial Hospital-Taipei between October 1988 and October 1999. RESULTS: Eight female patients with hepatic angiomyolipoma were identified, with ages ranging from 30 to 66 years (mean, 45.3 years). Abdominal pain was the most common symptom, occurring in six of eight patients (75%). Hepatocellular carcinoma was the most common preoperative diagnosis, occurring in three of eight patients (37.5%). Laparotomy was performed in seven of eight patients (87.5%). Among these seven patients, three patients (43%) received hepatic resection with 100% cure rate to date. One of the eight patients (12.5%) was closely follow up after diagnosis made by echo-guided needle biopsy. CONCLUSIONS: Hepatic angiomyolipoma is a rare and benign entity. It has a wide variation and poses a diagnostic challenge clinically, radiologically, and pathologically. Its prognosis is good regardless of management, including hepatic resection or conservative treatment after tissue biopsy by echo-guided needle. To alleviate the mass effect, surgical resection may be needed for hepatic angiomyolipoma in selected cases.

Abdominal Pain↗

Observations on serum 25-hydroxyvitamin D and calcium concentrations from wild-caught and captive neotropical bats, Artibeus jamaicensis.

Most bats of the suborder Microchiroptera are nocturnal, actively avoid sunlight, and eat mineral-poor diets. In those bats previously studied with respect to mineral metabolism, extensive bone remodeling occurs, and it has been suggested that calcium has been an important constraint on reproduction. There have been no previous studies of vitamin D or its metabolites in microchiropteran bats with respect to calcium metabolism. Reported is the utilization of current advances for the determination of serum levels of the vitamin D metabolite 25-hyroxyvitamin D (25-OH-D) in a neotropical bat, Artibeus jamaicensis. Serum from wild-caught animals contained low levels of 25-OH-D (5.6 +/- 3.0 ng/ml, n = 8). Bats maintained on a vitamin-D-supplemented diet had higher serum 25-OH-D levels and when the diet containing vitamin D was discontinued, mean serum 25-OH-D levels declined significantly after 6 months. Serum calcium concentrations in wild-caught bats (8.5 +/- 0.4 mg%) showed very little variation and were not significantly different in any of the vitamin-D-supplemented animals. A pairwise correlation analysis between 25-OH-D and serum calcium levels revealed no linear correlation. The results indicate either that 25-OH-D does not appear to play a key role or that low levels of 25-OH-D may be adequate in regulating serum calcium levels in this bat.

25-Hydroxyvitamin D 2↗

Hepatocellular carcinoma associated with focal nodular hyperplasia. Report of a case with clonal analysis.

We describe a hepatocellular carcinoma partially surrounded by focal nodular hyperplasia in a 65-year-old female patient. In order to clarify the relationship of the hepatocellular carcinoma and the adjacent focal nodular hyperplasia, clonal analysis was conducted. The clonal analysis was based on the methylation pattern of the polymorphic X-chromosome-linked androgen receptor gene (HUMARA). The allelic bands from the amplification of the focal nodular hyperplasia and of the hepatocellular carcinoma showed a significant reduction in the intensity of one of the two alleles as compared with two alleles of equal intensity in the buff coat after HhaI digestion, which indicated that these two parts were monoclonal. However, the inactivated allele in the focal nodular hyperplasia and that in the hepatocellular carcinoma were not identical. Therefore, the focal nodular hyperplasia and hepatocellular carcinoma probably derived from the clonal expansion of two different clones.

Aged↗

Brimonidine 0.2% versus apraclonidine 0.5% for prevention of intraocular pressure elevations after anterior segment laser surgery.

OBJECTIVE: To compare the efficacy of brimonidine 0.2% with apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. DESIGN: Double-masked, randomized clinical trial. PARTICIPANTS: Sixty-six patients underwent either laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:yttrium-aluminum-garnet laser capsulotomy. INTERVENTION: Eyes received either one drop of brimonidine 0.2% or apraclonidine 0.5% before laser surgery. MAIN OUTCOME MEASURES: Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. RESULTS: Before the laser treatment, 33 patients (50.0%) received brimonidine 0.2% and 33 patients (50.0%) received apraclonidine 0.5%. Eight of 33 patients (24.2%) in the brimonidine-treated group and 9 of 33 patients (27.3%) in the apraclonidine group had postoperative IOP increases of 5 mmHg or more. This was not statistically different (P = 0.80). By the time of last follow-up examination, 3 of 33 patients (9.1%) in the brimonidine-treated group and 3 of 33 patients (9.1%) in the apraclonidine group had IOP increases of 10 mmHg or more. This was also not statistically different (P > or = 0.95). The mean IOP reduction from baseline in the brimonidine group (-2.8 +/- 2.8 mmHg) was not statistically different (P = 0.55) compared with the mean IOP reduction in the apraclonidine group (-3.6 +/- 3.3 mmHg). There were no statistically significant changes in mean heart rate or blood pressure in either group except for a slight reduction in diastolic blood pressure at 1 hour (P = 0.005) in the brimonidine group (-5.2 +/- 7.4 mmHg) compared with the apraclonidine group (-0.2 +/- 6.4 mmHg). There were no clinically significant side effects noted in either group. CONCLUSIONS: A single preoperative drop of brimonidine 0.2% is as effective as apraclonidine 0.5% in preventing IOP elevation immediately after anterior segment laser surgery.

Adrenergic alpha-Agonists↗

Follicular dendritic cell tumor of the liver: a clinicopathologic and Epstein-Barr virus study of two cases.

Two cases of hepatic follicular dendritic cell (FDC) tumor are described. Both patients were female, aged 57 and 51 years. They presented with epigastralgia or abdominal fullness and weight loss. The first patient refused surgical resection. She developed progressive polyclonal gammopathy and then bilateral purpura over the legs. Skin biopsy revealed leukocytoclastic vasculitis with granular vascular deposits of IgA and C3. The second patient had marked peripheral blood and tissue eosinophilia. The histological diagnosis was confirmed by positive staining for CD21 and CD23. The stromal lymphocytes were predominantly composed of CD3(+)and CD8(+) cells. In situ hybridization for EBER showed a positive nuclear signal in tumor cells but not in inflammatory cells. Polymerase chain reaction amplification for Exon 3 of the latent membrane protein-1 (LMP-1) gene showed a characteristic 30-bp deletion between nucleotides 168282 and 168253, corresponding to the B95-8 sequence. The unique clinicopathological features of our cases have not been reported for FDC tumors before. The clinical significance of the 30-bp deletion in Exon 3 of the LMP-1 gene in FDC tumor of the liver warrants further investigation.

Complement C3↗

Intrahepatic cholangiocarcinoma with lymphoepithelioma-like component.

We present two cases of intrahepatic cholangiocarcinoma with lymphoepithelioma-like component. The patients included one woman and one man, aged 67 and 41 years, respectively. They presented with right upper quadrant pain and epigastralgia. Histologically, both tumors showed two distinct histological patterns with dense lymphoplasma cell infiltration. The first pattern was a well to moderately differentiated adenocarcinoma; the second component showed a feature similar to lymphoepithelioma-like carcinoma. Granulomatous reaction was noted in one case. Immunohistochemical study revealed that both tumors were immunoreactive with AE1/AE3, cytokeratin 7, and cytokeratin 19 but negative for carcinoembryonic antigen and cytokeratin 20. The stromal lymphocytes were composed of predominantly CD3(+) T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA (EBER) showed positive nuclear signal in tumor cells but not in inflammatory cells in one case. The presence or absence of EBV genome was confirmed by polymerase chain reaction of LMP-1 gene in both cases. The LMP-1 gene also had a 30-bp deletion in Exon 3 as compared with the products from B95-8 cells. We further sequenced the PCR product and confirmed a 30-bp deletion between Nucleotide (nt) 168,282 and nt 168,253 corresponding to the B95-8 sequence. The clinical significance of 30-bp deletion in Exon 3 of the LMP-1 gene in lymphoepithelioma-like carcinoma of the liver warrants further investigation.

Adaptor Proteins, Signal Transducing↗

Enhancing 1 alpha-hydroxylase activity with the 25-hydroxyvitamin D-1 alpha-hydroxylase gene in cultured human keratinocytes and mouse skin.

1 alpha,25-Dihydroxyvitamin D(3) (1 alpha,25(OH(2))D(3)) and its analogs are used to treat psoriasis because of their potent antiproliferative activity. They have the potential for causing hypercalcemia, however, and patients often become resistant to the drug. We examined the feasibility of enhancing the cutaneous production of 1 alpha,25(OH(2))D(3) using a human 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase) plasmid. The 1 alpha-OHase gene was fused to the green fluorescent protein gene (1 alpha-OHase-GFP) driven by the cytomegalovirus promoter. Transfection of cultured normal human keratinocytes with the 1 alpha-OHase-GFP plasmid resulted in a marked increase in the expression of 1 alpha-OHase-GFP in the mitochondria. Transfection of keratinocytes with 1 alpha-OHase-GFP or 1 alpha-OHase plasmids in vitro enhanced the 1 alpha-OHase activity substantially and increased the sensitivity of the keratinocytes to the antiproliferative effect of 25(OH)D(3). The 1 alpha-OHase-GFP plasmid was topically applied to shaved C57/BL6 mice. Twenty-four hours after topical application, immunohistochemical analysis of the skin for 1 alpha-OHase-GFP revealed the presence of 1 alpha-OHase-GFP in the epidermis and epidermal appendages including the hair follicles. The results from this study offer a unique new approach for the topical treatment of hyperproliferative disorders such as psoriasis and skin cancer using the 1 alpha-OHase gene that could locally increase the production of 1 alpha,25(OH(2))D(3) without causing hypercalcemia or resistance.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Treatment of vitamin D deficiency due to Crohn's disease with tanning bed ultraviolet B radiation.

In Crohn's disease, severe skeletal demineralization, secondary hyperparathyroidism, and muscle weakness can occur. This may be caused by impaired vitamin D absorption, resulting from extensive intestinal disease and resection of duodenum and jejunum, where vitamin D is absorbed. We report a 57-year-old woman with a long history of Crohn's disease and short-bowel syndrome who had only 2 feet of small intestine remaining after 3 bowel resections. She was taking a daily multivitamin containing 400 IU of vitamin D(3) and was dependent on total parenteral nutrition that contained 200 IU of vitamin D and calcium (18 mEq in a 1-L bag infused over 8 hours daily) for a period of 36 months. Despite the above replacement, she complained of bone pain and muscle weakness, and she continued to be vitamin D-deficient with a 25(OH)D level <20 ng/mL. She was then exposed to ultraviolet B (UVB) radiation in a tanning bed wearing a 1-piece bathing suit for 10 minutes, 3 times a week for 6 months at the General Clinical Research Center, Boston University Medical Center. She tolerated the irradiation well without evidence of erythema. After 4 weeks, her serum 25(OH)D level increased by 357% from 7 to 32 ng/mL, parathyroid hormone level decreased by 52% from 92 to 44 pg/mL, and the serum calcium level increased from 7.8 to 8.5 mg/dL. After 6 months of UVB treatment, her serum 25(OH)D level was maintained in the normal range and was free of muscle weakness, and bone and muscle pain.

Bone and Bones↗

Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions.

The Reg I gene (regenerating gene) and its product (Reg protein) are a regenerating and/or proliferating factor(s) of pancreatic islet cells. The ectopic expression of REG Ialpha was shown in colorectal carcinomas, suggesting that REG Ialpha is related to their carcinogenesis. In this study, we examined the expression of REG I in intrahepatic cholangiocarcinoma (ICC) and its precursor lesion (biliary dysplasia). By polymerase chain reaction and in situ hybridization (ISH) studies using a total of 16 fresh liver specimens, REG Ialpha mRNA was demonstrated in 6 of 11 (55%) ICC cases, but in 0 of 5 (0%) normal livers. Immunohistochemistry for REG I protein was performed in 100 formalin-fixed, paraffin-embedded sections obtained from the 18 cases of ICC alone, 45 hepatolithiasis with ICC (n = 19) or biliary dysplasia (n = 26), 21 hepatolithiasis alone (all with hyperplasia), and 16 normal livers. In ICC, the expression of REG I protein was significantly dependent on the histologic differentiation; 12 of 13 (92%) cases in papillary and well-differentiated, 6 of 16 (38%) cases in moderately differentiated, and 0 of 8 (0%) cases in poorly differentiated types. Moreover, in the lesions of hyperplasia, low-grade dysplasia, and high-grade dysplasia in hepatolithiasis, REG I protein was expressed in 4 of 21 (19%), 7 of 12 (58%), and 13 of 14 (93%) cases, respectively. In normal liver, intrahepatic bile ducts were constantly negative for REG I protein. These findings suggest that neoexpression of REG I is a good marker for biliary mucosa at risk for development of ICC, and also that REG I plays a role in the early stages of biliary carcinogenesis, probably via a cell-proliferative effect.

Bile Duct Neoplasms↗

Intraductal papillary neoplasia of the liver associated with hepatolithiasis.

Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was found in 41 of 136 hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading and glandular involvement were commonly observed in all types. About half of types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN-L with goblet cells and colon-like metaplasia was frequently associated with overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric metaplasia and significant intraductal spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported "mucin-producing intrahepatic cholangiocarcinoma" with a favorable prognosis is included in IPN-L.

Adult↗

Effects of a 7-day eccentric training period on muscle damage and inflammation.

PURPOSE: This study examined the effects of a 7-d repeated maximal isokinetic eccentric training period on the indicators of muscle damage and inflammatory response. METHODS: Twenty-two college-age males were randomly assigned to eccentric training (ET) (N = 12) and control groups (CON) (N = 10). The initial exercise was 30 repetitions of maximal voluntary isokinetic eccentric contraction (ECC1) on nondominant elbow flexors with Cybex 6000 at 60 degrees.s-1 angular velocity. The ET group performed the same exercise for the following 6 consecutive days (referred to as ECC2 to ECC7) after ECC1. Upper arm circumference (CIR), range of motion (ROM), and maximal isometric force (MIF) were measured before, immediately after, and every 24 h for 7 consecutive days after ECC1. Plasma creatine kinase (CK), lactate dehydrogenase (LDH), glutamic oxaloacetate transaminase (GOT), leukocyte counts, and serum interleukin-1beta and -6 (IL-1beta, IL-6) levels were assessed before; at 2 h; and at 1, 3, 4, 6, and 7 d after ECC1. Muscle soreness was measured before and for 7 consecutive days after ECC1. RESULTS: The ECC1 produced significant changes in most of the measures for both groups (P < 0.05), with the exception of leukocyte counts (P > 0.05). No indicators of increased damage (P > 0.05) were found from ECC2 to ECC7 for the ET group. CONCLUSION: Continuous intensive isokinetic eccentric training performed with damaged muscles did not exacerbate muscle damage and inflammation after ECC1. In addition, a muscular "adaptation effect" may occur as early as 24 h after ECC1, as shown by the ET group's performance for 6 consecutive days after ECC1.

Adaptation, Physiological↗

Identification of a hepatic factor capable of supporting hepatitis C virus replication in a nonpermissive cell line.

Although hepatitis C virus E2 protein can bind to human cells by interacting with a putative viral receptor, CD81, the interaction alone is not sufficient to establish permissiveness for hepatitis C virus infection. Using an Epstein-Barr virus-based extrachromosomal replication system, we have screened through a human liver cDNA library and successfully identified a cDNA capable of supporting hepatitis C virus replication in an otherwise nonpermissive cell line. This cDNA encodes a protein exhibiting homology to a group of proteins derived from various evolutionarily distant species, including Oryza sativa submergence-induced protein 2A. The mRNAs encoding this factor are heterogeneous at the 5' ends and are ubiquitously expressed in multiple tissues, albeit in a very small amount. The longest mRNA contains an in-frame and upstream initiation codon and codes for a larger protein. This 5'-extended form of mRNA was detected in hepatocellular carcinoma, but not in normal liver tissue. Immunofluorescence analysis demonstrated that the hepatic factor was distributed evenly in cells, but occasionally formed aggregations in the peri- or intranuclear areas. In summary, we have identified a hepatic factor capable of supporting hepatitis C virus replication in an otherwise nonpermissive cell line. This factor belongs to a previously uncharacterized protein family. The physiological function of this protein awaits further study.

Amino Acid Sequence↗