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Biomedical subjects

J D Chen

Publications and source records attributed to J D Chen.

At least 19 recordsLinked to original sources

Effect of acute gastric electrical stimulation on the systemic release of hormones and plasma glucose in dogs.

This study evaluated the effect of gastric electrical stimulation (GES) with various parameters on plasma concentrations of satiety-related peptides and glucose. GES was performed in nine healthy dogs via electrodes implanted in the middle of the lesser curvature. Four sessions were performed in each animal: control, stimulation with IGS (implantable gastric stimulation for obesity, 0.3 m sec), modified IGS (2 msec), and long pulses (300 msec). Blood samples were collected at 15 and 0 min before the meal and at 15, 30, and 60 min after the meal. GES was initiated 30 min before the first blood sample and maintained throughout collection. Plasma ghrelin, leptin, insulin and glucose were measured. The total AUCs of plasma ghrelin and leptin were not significantly affected by GES. The total AUC of plasma insulin was significantly lower with IGS and long pulse parameters (P < 0.05). The total AUC for plasma glucose was significantly lower in sessions with long pulses and modified IGS parameters (P < 0.05). We conclude that acute GES is able to change the release of some satiety-related peptides. Whether this is associated with the changed eating behavior and weight loss in obese patients needs further investigation.

Animals↗

Genetic diversity of avian infectious bronchitis coronavirus strains isolated in China between 1995 and 2004.

Twenty-six avian infectious bronchitis (IB) viruses (IBV) were isolated from outbreaks in chickens in China between 1995 and 2004. They were characterized by comparison with twenty-six Chinese reference strains and five other IBV strains. Chinese IBVs, which were mainly nephropathogenic, were placed into seven genotypes. Fourteen Chinese IBV isolates were placed in genotype I, having small evolutionary distances from each other. Genotype II included 6 strains that were isolated in the 1990s in China. Genotype III consisted of eight Chinese isolates that showed close relationship with Korean IBV isolates. Another eight IBV isolates clustered in genotype IV and showed larger evolutionary distances. The Massachusetts serotype was present in China in 1990s and was in a separate genotype. Two isolates, HN99 and CK/CH/LHN/00I, which might be a reisolation of vaccine strains, clustered into genotype VI. Four Chinese IBV isolates formed another genotype and showed larger evolutionary distances from other Chinese IBV genotypes (genotype VII). IBVs in same genotypes showed more than 90% amino acid sequence similarities, whereas most of the viruses in different genotypes showed less than 90%. The results showed that IBVs in China came from genetic changes both in IBV populations that existed before the advent of vaccination and in the viruses that were introduced through live vaccines. IBVs showing various genetic differences are cocirculating in China.

Animals↗

Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond. METHODS: The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank). FINDINGS: Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse. INTERPRETATION: The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.

Canada↗

Hyperparathyroidism-jaw tumour syndrome.

Amongst hyperparathyroidism-related syndromes, hyperparathyroidism-jaw tumour syndrome is one of the least common and relatively unknown but its clinical and genetic aspects are not less interesting or important. With the recent identification of its genes, we can now better characterize the disease, both clinically and genetically, which will certainly impact the field of endocrinology and oncology. In this article, we review the clinico-pathological features and genetic basis of this syndrome with the hope that it will create awareness and interest in this disease amongst clinicians and basic scientists.

Genes, Tumor Suppressor↗

The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39).

The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5' RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.

3' Untranslated Regions↗

HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

Adenoma↗

Painting of fourth, a chromosome-specific protein in Drosophila.

Chromosome-specific gene regulation is known thus far only as a mechanism to equalize the transcriptional activity of the single male X chromosome with that of the two female X chromosomes. In Drosophila melanogaster, a complex including the five Male-Specific Lethal (MSL) proteins, "paints" the male X chromosome, mediating its hypertranscription. Here, with the molecular cloning of Painting of fourth (Pof), we describe a previously uncharacterized gene encoding a chromosome-specific protein in Drosophila. Unlike the MSL proteins, POF paints an autosome, the fourth chromosome of Drosophila melanogaster. Chromosome translocation analysis shows that the binding depends on an initiation site in the proximal region of chromosome 4 and spreads in cis to involve the entire chromosome. The spreading depends on sequences or structures specific to chromosome 4 and cannot extend to parts of other chromosomes translocated to the fourth. Spreading can also occur in trans to a paired homologue that lacks the initiation region. In the related species Drosophila busckii, POF paints the entire X chromosome exclusively in males, suggesting relationships between the fourth chromosome and the X and between POF complexes and dosage-compensation complexes.

Amino Acid Sequence↗

SMRTE inhibits MEF2C transcriptional activation by targeting HDAC4 and 5 to nuclear domains.

The silencing mediator for retinoic acid and thyroid hormone receptors (SMRT) mediates transcriptional repression by recruiting histone deacetylases (HDACs) to the DNA-bound nuclear receptor complex. The full-length SMRT (SMRTe) contains an N-terminal sequence that is highly conserved to the nuclear receptor corepressor N-CoR. To date, little is known about the activity and function of the full-length SMRTe protein, despite extensive studies on separated receptor interaction and transcriptional repression domains. Here we show that SMRTe inhibits MEF2C transcriptional activation by targeting selective HDACs to unique subnuclear domains. Indirect immunofluorescence studies with anti-SMRTe antibody reveal discrete cytoplasmic and nuclear speckles, which contain RARalpha in an RA-sensitive manner. Formation of the SMRTe nuclear speckles results in recruitment of several class I and class II HDACs to these subnuclear domains in a process depending on HDAC enzymatic activity. Intriguingly, although HDAC4 is located primarily in the cytoplasm, coexpression of SMRTe dramatically translocates HDAC4 from the cytoplasm into the nucleus, where HDAC4 prevents MEF2C from activating muscle differentiation. SMRTe also translocates HDAC5 from diffusive nucleoplasm into discrete nuclear domains. Accordingly, SMRTe synergizes with HDAC4 and 5 to inhibit MEF2C transactivation of target promoter, suggesting that nuclear domain targeting of HDAC4/5 may be important in preventing muscle cell differentiation. These results highlight an unexpected new function of the nuclear receptor corepressor SMRTe for its role in regulating cellular trafficking of nuclear receptor and selective HDACs that may play an important role in regulation of cell growth and differentiation.

Active Transport, Cell Nucleus↗

The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor.

Steroid/nuclear hormone receptors are ligand-dependent transcriptional regulators that control gene expression in a wide array of biological processes. The transcriptional activity of the receptors is mediated by an N-terminal ligand-independent transcriptional activation function AF-1 and a C-terminal ligand-dependent transcriptional activation function AF-2. The nuclear receptor coactivator RAC3 (also known as AIB1/ACTR/pCIP/TRAM-1/SRC-3) is amplified in breast cancer cells, where it forms a complex with estrogen receptor (ER) and enhances AF-2 activity of the receptor. Here, we identify a putative human homologue of the yeast DNA repair and transcriptional regulator MMS19 as a RAC3-interacting protein. The human MMS19 interacts with the N-terminal PAS-A/B domain of RAC3 in vivo and in vitro through a conserved C-terminal domain. Interestingly, the human MMS19 also interacts with estrogen receptors in a ligand-independent manner but not with retinoic acid receptor or thyroid hormone receptor. Overexpression of the interacting domain of hMMS19 strongly inhibits ER-mediated transcriptional activation, indicating a dominant negative activity. In contrast, over expression of the full-length hMMS19 enhances ER-mediated transcriptional activation. We find that hMMS19 stimulates the AF-1 activity of ERalpha, but not the AF-2 activity, suggesting that hMMS19 may be an AF-1-specific transcriptional coactivator of estrogen receptor.

Amino Acid Sequence↗

Role of retinoid receptor coactivator pockets in cofactor recruitment and transcriptional regulation.

The nuclear receptor for retinoic acid (RAR) forms a heterodimeric complex with the retinoid X receptor (RXR). This RXR/RAR heterodimer binds to the promoter of retinoic acid target genes and recruits coactivators and corepressors to regulate gene expression. Currently, the relative role of each receptor monomer in regulating coactivator and corepressor recruitment remains unclear. Here we show that the receptor-associated coactivator 3 (RAC3) uses two separate LXXLL motifs to bind RAR and RXR. The mutation of the coactivator-binding pockets of RAR and RXR abolishes RAC3 binding. Although the coactivator pocket of RXR is essential for the function of the RXR homodimer, it has a minor role for the recruitment of RAC3 and trans-activation by the RXR/RAR heterodimer. Consistently, deletion of the activation helix of RXR enhances binding of RAC3 to the heterodimer, and mutation of the coactivator pocket of RXR had little effect on RXR/RAR activity. In contrast, the coactivator pocket and the activation helix of RAR are absolutely required. We also show that different residues of the RAR coactivator pocket are used differently for interactions with the corepressor silencing mediator for retinoid and thyroid hormone receptor (SMRT) and coactivator. These results indicate a differential role for each retinoid receptor to the overall binding of cofactors and regulation of transcription by the retinoid receptor heterodimer.

Amino Acid Motifs↗

Sonography of acute right side colonic diverticulitis.

BACKGROUND: To describe the prevalence and sonographic findings and ultrasound diagnostic accuracy of the right side colonic diverticulitis in patients having right lower abdominal pain with indeterminate nature. METHODS: A total of 934 patients with acute right lower abdominal pain of clinically indeterminate nature were referred for ultrasound examination (US). US studies were performed with 3.5 to 7.0 (or occasionally 10) MHz transducers using graded compression method. Twenty-three patients were finally diagnosed to have an uncomplicated acute diverticulitis of the right colon. The gray-scale sonographic images were reviewed. A retrospective study was undertaken to evaluate diagnostic contribution of US. RESULTS: The prevalence of acute right side colonic diverticulitis was 2.5% in patients with clinically indeterminate acute right lower abdominal pain. Locations of the inflamed diverticula include cecum in 6 patients, proximal ascending colon in 15 patients, and distal ascending colon in only 2 patients. Sonography detected 21 inflamed diverticula with 1 false positive and 2 false negative results. The most typical sonographic feature of an inflamed diverticulum of right side colon was a rounded or oval-shaped hypoechoic or nearly anechoic structure (52%) protruding out from the segmentally thickened colonic wall. Some of them might contain strong echoes representing gas or feces (43%), or stone in the lumen (5%). Regional pericolic or peridiverticular fat thickening was noted in 57% of patients, and segmental colon wall thickening in 38%. US examination yielded a sensitivity of 91.3%, a specificity of 99.8%, an overall accuracy of 99.5%, a positive predictive value of 95.5%, and a negative predictive value of 99.7%. A positive sonogram made the likelihood of acute right side diverticulitis 456.5 times greater compared with the pretest clinical impression. US differentiated acute right side colonic diverticulitis from acute appendicitis with a 100% accuracy. CONCLUSIONS: Ultrasound can be extremely useful in diagnosing acute right side colonic diverticulitis. Careful ultrasound evaluation of the right colon and the cecum may facilitate a correct diagnosis and help differentiate from acute appendicitis, and steer the surgeon to a more effective management.

Acute Disease↗

Clonidine inhibits postprandial response of antral myoelectrical activity.

Clonidine, an alpha2-adrenergic agonist, is known to inhibit gastric motility and delay gastric emptying in both humans and animals, but its effect on gastric myoelectric activity is unclear. The aim of this study was to investigate the effect of clonidine on postprandial gastric myoelectric activity. The experiment was performed in eight hound dogs (14.5-22.6 kg) implanted with three pairs of bipolar serosal electrodes with an interval of 4 cm and the most distal pair 2 cm above the pylorus. Each dog was studied twice on two separate days after a complete recovery from surgery. Gastric myoelectrical activity was recorded for 30 min in the fasting state and 90 min after a solid test meal of 838 kcal. Two tablets of clonidine (0.4 mg) were given with the meal in one of the sessions. The dominant frequency and power of the slow waves from the most distal pair were calculated by computerized spectral analysis. All data were expressed as mean +/- SE. A significant postprandial increase in the dominant power of the slow wave and an increase in the percentages of gastric slow waves with spike bursts were observed in the control session, whereas the dominant frequency of gastric slow waves showed a significant postprandial decrease after the meal. The dominant power increased 8.24+/-0.5, 8.6+/-0.2, and 7.5+/-0.3 dB, respectively, in the first, and second, and third 30-min period after the meal (all P < 0.01 vs baseline). Clonidine completely abolished the postprandial increase in the dominant power of the gastric slow wave and significantly inhibited spike bursts. The dominant power only increased 2.4+/-1.1 dB (P > 0.05 vs baseline; P < 0.01 vs the first postprandial period in the control session), 0.6+/-1.5 dB (P > 0.05 vs baseline; P < 0.05 vs the second postprandial period in the control session) and -1.5+/-2.2 dB (P > 0.05 vs baseline; P < 0.05 vs the third postprandial period in the control session) respectively during the first, second, and third periods after the meal and clonidine. However, it did not affect the postprandial change of the dominant frequency of gastric slow waves. No significant changes in percentage of regular slow waves were noted with the meal or with clonidine (P > 0.05). In conclusion, the postprandial response of gastric myoelectrical activity in dogs to a solid meal is featured with an increase in amplitude and spike bursts, which is inhibited by clonidine.

Adrenergic alpha-Agonists↗

Intestinointestinal inhibitory reflexes: effect of distension on intestinal slow waves.

The motor response induced by intraluminal distension of the small intestine has been well investigated. However, little is known of the myoelectrical response to intraluminal distension. The aim of this study was to investigate the effects of oral- and anal-side distension on jejunal slow waves in dogs. The study was performed in 10 healthy female hound dogs implanted with three pairs of electrodes on the jejunum and an intestinal fistula. The first study session was designed to investigate the effects of anal-side distension on jejunal myoelectrical activity in fasting state. The protocol consisted of a 30-min baseline recording, a 30-min recording during anal-side balloon distension located 5 cm distal to the most distal pair of electrodes, and another 30-min recording after distension. The second session was designed to investigate the effect of oral-side distension with the balloon 5 cm proximal to the most proximal pair of electrodes. Jejunal slow waves were severely impaired by both anal- and oral-side distension. The dominant power was significantly reduced from -2.96 +/- 0.90 dB at baseline to -6.00 +/- 0.64 dB during anal-side distension (P < 0.0005) and from -3.90 +/- 0.85 dB at baseline to -7.17 +/- 0.90 dB during oral-side distension (P < 0.001). The percentage of normal 17 to 22-cpm slow waves was significantly decreased from 97.39 +/- 0.88% to 83.48 +/- 3.12% during anal-side distension (P < 0.0005) and from 92.49 +/- 2.42% to 68.80 +/- 7.24% during oral-side distension (P < 0.002). The percentage of slow wave coupling was decreased from 95.08 +/- 2.27% to 52.48 +/- 7.73% during anal-side distension (P < 0.0005) and from 84.82 +/- 6.75% to 49.21 +/- 8.91% during oral-side distension (P < 0.001). The instability coefficient of the dominant frequency was significantly increased during anal-side distension. In conclusion, intraluminal distension of the jejunum severely impairs jejunal slow waves. The slow waves on both sides of distension become less coupled, less regular, and are of lower amplitude.

Animals↗

Postprandial improvement of gastric dysrhythmias in patients with type II diabetes: identification of responders and nonresponders.

Using the technique known as electrogastrography, we studied the postprandial response of gastric myoelectrial activity in subjects with type II diabetes. Seventy-one subjects with type II diabetes underwent 1 hr of fasting electrogastrography recording. HbA1c and fasting serum glucose levels were obtained. Subjects then underwent an additional 2 hr of electrogastrography recording in the post prandial state. Sixty of the 71 patients (85%) had gastric rhythm abnormalities in the fasting state. Forty-six of 71 subjects (65%) responded to the test meal by improving their electrogastrography tracings (responders) while 35% did not respond (nonresponders). The time spent in bradygastria during the fasting state by responders was 26.3+/-12.8% vs 10.9+/-8.5% for nonresponders (P < 0.0001). The percent tachygastria during the fasting state in responders was 19.8+/-13.0%, which was less than nonresponders (38.3+/-29.7%) (P < 0.001). Fasting plasma glucose and HbA1c could not be used to predict the gastric myoelectrical response to meal. In conclusion, gastric rhythm disturbances are common in type II diabetes; there was no correlation between HbA1c levels, age, duration of diabetes, or fasting serum glucose and gastric dysrhythmia in response to meal; two groups of subjects emerged: those who became less dysrhythmic in the post pradial state (responders) and those who did not (non-responders); and fasting bradygastria was associated with responders and fasting tachygastria was associated with nonresponders.

Diabetes Mellitus, Type 2↗

Prevalence of gastric myoelectrical abnormalities in patients with nonulcer dyspepsia and H. pylori infection: resolution after H. pylori eradication.

The aims of this study were to investigate the effects of H. pylori eradication on gastric myoelectrical activity and dyspeptic symptoms. Sixty-two subjects with H. pylori infection and no active peptic ulcer participated in this study, which involved three sessions. Anti-H. pylori therapy consisting of clarithromycin and omeprazole was given for two weeks. Gastric myoelectrical activity was measured using surface electrogastrography and dyspeptic symptoms were scored at each session. A [14C] urea breath test was performed at baseline and one month after treatment. In comparison with baseline, the percentage of normal slow waves was significantly increased and the mean total symptom score was significantly reduced one and three months after therapy (P < 0.05). Approximately 40% of patients with nonulcer dyspepsia' symptoms and H. pylori infection have abnormal gastric myoelectrical activity, which may be normalized following the eradication of H. pylori infection. The normalization of gastric myoelectrical activity may be one explanation for the significant symptom improvement in this subset of the dyspepsia population after H. pylori eradication.

Adult↗

Acinar cell carcinoma with hypervascularity.

Acinar cell carcinoma is an uncommon malignancy with a reported incidence of 1% among exocrine tumors of the pancreas. The case of a 60-year-old Taiwanese man who presented with obstructive jaundice, abdominal pain, and body weight loss is described here. A mixed clinical picture of islet cell tumor and ductal carcinoma of the pancreas was shown to be a hypervascular tumor at the pancreatic head region with an irregular stricture at the common channel of the common bile and pancreatic ducts. The patient had normal levels of plasma carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, but an increase in plasma levels of insulin and C-peptide. Immunohistochemical stains and electron microscopic examination of the tumor was consistent with acinar cell carcinoma.

Carcinoma, Acinar Cell↗

Post-partum acute exacerbation of chronic hepatitis in a hepatitis C-carrier mother.

Hepatitis C virus infection is a global health problem; however, the interaction between pregnancy and chronic hepatitis C remains controversial. A Taiwanese woman with chronic hepatitis C had an uncomplicated pregnancy and gave birth to a female baby through spontaneous vaginal delivery. The serum levels of alanine aminotransferase and hepatitis C virus (HCV) RNA were measured before pregnancy, in the first and third trimesters, 1 and 3 months after delivery, respectively. During her pregnancy, the serum aminotransferase levels became normalized, while the serum HCV-RNA levels declined significantly and consecutively with the lowest viral load in the third trimester. One month after delivery, she had an abrupt elevation of serum HCV-RNA level, paralleling a hepatitis flare with serum aminotransferase level more than 20-fold the upper normal limit. The serum HCV-RNA levels declined thereafter, and serum aminotransferase levels became normalized 3 months postdelivery. She was infected with HCV genotype 1a throughout the entire follow-up period, and other causes of hepatitis flare were excluded. In conclusion, post-partum acute exacerbation of chronic hepatitis may occur in HCV-carrier mothers, and an abrupt elevation of serum HCV-RNA level may be associated with the acute exacerbation.

Acute Disease↗