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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 91 records · Page 5Linked to original sources

CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in U.S. physicians.

BACKGROUND: CAG repeat length in exon 1 of the androgen receptor (AR) gene correlates inversely with transcriptional transactivation activity of the AR. Men with shorter AR CAG repeat lengths are at higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that a shorter AR gene CAG repeat length increases the risk of developing of BPH. METHODS: Among 14,916 men of the Physicians' Health Study who had provided a blood sample in 1982, we measured AR gene CAG repeat lengths for 310 men who had surgery for BPH up to 7.5 years of follow-up and 1,041 controls. RESULTS: Risk of surgery for BPH increased linearly with decreasing AR CAG repeat length (P (trend) = 0.03). Relative to men with a CAG repeat length > or = 25, men with a repeat length < or = 19 had an odds ratio of BPH surgery of 1.76 (95% confidence interval, 1.16-2.65). CONCLUSIONS: Variability in the AR gene CAG repeat influences the development of symptomatic BPH.

Humans↗

Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome. Genes Chromosomes Cancer 25:75-81, 1999.

Chan TL, Yuen ST, Chung LP, Ho JWC, Kwan K, Fan YW, Chan ASY, Leung SY. 1999. Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome. Genes Chromosomes Cancer 25:75-81, 1999. It has come to our attention that the three patients described in the article above, were also included in a report by Leung et al., American Journal of Pathology, 153:1181-1189, 1998. Reference to the American Journal of Pathology article was inadvertently omitted

Journal Article↗

Cardiac Neoplasms.

Surgical resection is usually the only form of curative therapy available for primary cardiac neoplasms. Benign tumors can often be completely removed with few complications and a low mortality rate, but complete resection is possible for fewer than half of primary malignant tumors. Radiation therapy plays an adjunct and palliative role in treatment. The outcome of chemotherapy, the dominant treatment method, is poor. Sarcomas are inherently chemoresistant and show a response rate of less than 50%. Lymphomas present late and respond poorly. Cardiectomy and cardiac transplantation may cure unresectable benign cardiac tumors or, rarely, malignant ones.

Journal Article↗

The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia.

OBJECTIVES: Shorter CAG repeat lengths in exon 1 of the androgen receptor (AR) gene are associated with a stronger transcriptional activity of the AR and with a higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that men with shorter AR gene CAG repeat lengths have an increased risk of developing BPH. METHODS: Using data from the Health Professionals Follow-up Study (HPFS), we evaluated the relationship between AR gene CAG repeat length and prevalent BPH, as defined by BPH surgery, by enlarged prostate gland detected by digital rectal examination, and by urinary symptoms as determined by the American Urological Association Symptom Index. RESULTS: The odds ratio for BPH surgery or enlarged prostate gland was 1.92 (95% confidence interval [CI] 1.22 to 3.03; P [trend] = 0.0002), comparing AR gene CAG repeat length of 1 9 or less to 25 or more. Results were similar for the end points of BPH surgery (P [trend] = 0.002) and for enlarged prostate gland (P [trend] = 0.001). For a six-repeat decrease in CAG repeat length, the odds ratio for having moderate or severe urinary obstructive symptoms from an enlarged prostate gland was 3.62 (95% CI 1.51 to 8.67; P = 0.004). CONCLUSIONS: Variability in the AR gene CAG repeat influences the development of symptomatic BPH, particularly in predicting obstructive urinary symptoms. Our findings support further study to establish the appropriate clinical relevance.

Adult↗

An aldose reductase intragenic polymorphism associated with diabetic retinopathy.

The polyol pathway has been considered important in the development of diabetes long-term complications. Diabetic patients with microvascular disease have increased gene expression and enzyme activity, which may be due to variants in the aldose reductase gene. An association of an intragenic BamHI polymorphic site with diabetic retinopathy and nephropathy has been suggested, but the BamHI site has not been confirmed. In the current study, long template PCR-RFLP and DNA sequencing were used to ascertain its existence. A single substitution of A to C at 95th nucleotide of intron 8 was identified. This polymorphism was investigated in 164 adolescents with type 1 diabetes in whom diabetic retinopathy was assessed by stereoscopic retinal photography. Both the wild haplotype B and homozygote BB were significantly more common in the adolescents with retinopathy than in those without retinopathy (P = 0.018 and 0.002, respectively). We also confirmed an association between a previously described (CA)n repeat sequence and retinopathy in these adolescents (P < 0.0005). However, there was no association between the two polymorphisms.

Adolescent↗

Self-expandable metal stents for malignant dysphagia.

BACKGROUND: The use of self-expandable metal stents in relieving dysphagia for patients with incurable malignant oesophageal strictures was retrospectively evaluated. METHODS: Between September 1993 and August 1996, 66 male and 16 female patients with a median age of 72 years received self-expandable metal stents for malignant dysphagia. Six patients had concurrent tracheo-oesophageal fistulas. All patients were stented under sedation and stent insertion was performed under fluoroscopic guidance. RESULTS: Stent placement was successful in 80 patients (98%). There were seven early complications (inaccurate positioning (n = 3), migration (n = 1), incomplete expansion (n = 1), intractable pain (n = 1), and perforation (n = 1)). Two complications were lethal and three were treated endoscopically. Mean dysphagia grade improved from 3.2+/-0.7 to 1.8+/-0.9 (P < 0.05) after implantation. All tracheo-esophageal fistulas were successfully occluded. Upon a median follow-up of 8 weeks (range: 2-20 weeks), 30 complications developed in 21 patients (tumour overgrowth (n = 15), food bolus obstruction (n = 7), tumour ingrowth (n = 2), buckling of stent (n = 2), tracheo-esophageal fistula (n = 2), bleeding (n = 1), and gastric wall herniation through metal coils (n = 1)). Median survival was 13 weeks (range: 1-82 weeks). CONCLUSION: Self-expandable metal stents provide useful palliation in patients with incurable malignant dysphagia.

Adenocarcinoma↗

Optimization strategies for production of mammalian embryos by nuclear transfer.

In order to optimize each of the individual steps in the nuclear transfer procedure, we report alternative protocols useful for producing recipient cytoplasts and for improving the success rate of nuclear transfer embryos in cattle, rhesus monkey, and hamster. Vital labeling of maternal chromatin/spindle is accomplished by long wavelength fluorochromes Sybr14 and rhodamine labeled tubulin allowing constant monitoring and verification during enucleation. The use of Chinese hamster ovary (CHO) donor cells expressing the viral influenza hemagglutinin fusion protein (HA-300a+), to adhere and induce fusion between the donor cells and enucleated cow, rhesus and hamster oocytes was examined. Cell surface hemagglutinin was activated with trypsin prior to nuclear transfer and fusion was induced by a short incubation of a newly created nuclear transfer couplet at pH 5.2 at room temperature. Donor cell cytoplasm was dynamically labeled with CMFDA, or further transfected with the green fluorescence protein (GFP) gene, so that fusion could be directly monitored using live imaging. High rates of fusion were observed between CHO donor cells and hamster (100%), rhesus (100%), and cow recipient cytoplasts (81.6%). Live imaging during fusion revealed rapid intermixing of cytoplasmic components between a recipient and a donor cell. Prelabeled donor cytoplasmic components were uniformly distributed throughout the recipient cytoplast, within minutes of fusion, while the newly introduced nucleus remained at the periphery. The fusion process did not induce activation as evidenced by unchanged distribution and density of cortical granules in the recipient cytoplasts. After artificial activation, the nuclear transfer embryos created in this manner were capable of completing several embryonic cell divisions. These procedures hold promise for enhancing the efficiency of nuclear transfer in mammals of importance for biomedical research, agriculture, biotechnology, and preserving unique, rare, and endangered species.

Animals↗

Increased potency of an aptameric G-rich oligonucleotide is associated with novel functional properties of phosphorothioate linkages.

We previously showed that inhibition of the expression of CD28 (an essential immune receptor on T cells) mediated by a phosphorothioate (PS)-modified aptameric oligodeoxynucleotide (ODN) sequence, GR1, resulted in reduced T cell responses in vitro and in vivo. Using GR1 sequences differing only in the amount of terminal PS linkages (chimeric SO-ODN), the present study demonstrated that even after a substantial reduction in PS linkages, this 18-mer ODN sequence could still confer functionality in the ODN-mediated inhibition of CD28 expression. We showed that secondary structure and full retention of the ability to form a specific protein-ODN complex and to increase cellular uptake in activated Jurkat T cells were critical parameters in the determination of the magnitude of bioactivity of chimeric SO-ODN. We report that a chimeric SO-ODN with terminal PS linkages that total 9 (ICN 17221) or 12 (ICN 17263) was sufficient to inhibit CD28 expression and suppress in vivo inflammatory ear responses to contact allergen in mice with similar potency to the 17-thioate S-ODN (ICN 16064). Interestingly, all chimeric SO-ODN showed similar in vitro nuclease resistance. These data suggest alternate functional properties for PS linkages, unrelated to nuclease resistance, in enhancing the bioactivity of a G-rich aptamer.

Animals↗

6-Hydroxydopamine induced cardiac malformations and alterations of the autonomic nervous system in the developing chicken embryo.

6-Hydroxydopamine (6-OHDA) was injected into the air sac of developing chicken embryos on day E3 in order to study its effects on cardiac development both morphologically and biochemically. A dose-dependent teratogenic effect and fetotoxicity were observed in the 6-OHDA-treated embryos. Cardiac malformations, including ventricular septal lesions, detachment of the apical portions of the ventricles, cardiac hypertrophy, areas of coagulative necrosis with pyknotic nuclei and broken nuclear membranes, and swollen mitochondria were evident from gross histologic and ultrastructural examinations. A LD50 of 0.3 mg/egg on day E11 was obtained. Biochemically, 6-OHDA induced a significant dose-dependent reduction in the total cardiac choline acetyltransferase (ChAT) activities on days E8 and E11, followed by a recovery on days E15 and E20. The effects on muscarinic acetylcholine receptors (mAChRs) were less marked than on ChAT, indicating the effects on the cholinergic nervous system development are primarily presynaptic. There was a significant decrease in the level of norepinephrine (NE) and a delay in the appearance of detectable cardiac NE. It is suggested that 6-OHDA-induced cardiac malformation can be a useful model to study the mechanisms of cardiovascular development.

Adrenergic Agents↗

China's "market economics in command": footwear workers' health in jeopardy.

This study of occupational safety and health (OSH) problems in the footwear industry in China, the world's largest shoemaker, is based on four years of research in China supplemented by research in Taiwan, Australia, and the United States. With the advent of the economic reforms of the early 1980s, the Chinese state is being driven by an economic imperative under which the profit motive overrides other concerns, causing a deterioration in OSH conditions. Footwear workers are being exposed to high levels of benzene, toluene, and other toxic solvents contained in the adhesives used in the shoe-making process. Many workers have been afflicted with aplastic anemia, leukemia, and other health problems. Most of China's current permissible exposure limits to toxins are either outdated or underenforced. As a result, the Chinese state's protection of footwear workers' health is inadequate. The article aims to draw the attention of the international OSH community to the importance of setting specific exposure standards for the footwear industry worldwide.

China↗

Comparison of palliative care needs of English- and non-English-speaking patients.

This study examined whether patients who are not fluent in English receive less than optimal palliative care. The subjects were 130 consecutive patients (24 non-English speakers, NE, and 106 English speakers, E) with advanced malignant disease who were admitted to three metropolitan-area hospitals and followed for 6 months or until death. 92% of patients who were unaware of their diagnosis were NE. Control of non-pain symptoms was worse for NE patients than for E patients during their last two months. There was an increased prevalence of mood disturbance in NE patients during their first two months in the study. Of the 102 (83 E, 19 NE) patients who died during the study period, no NE patients died at home. These results suggest that patients not fluent in English received less optimal palliative care. Communication of the diagnosis and prognosis requires the cooperation of the patients' families as well as the use of professional interpreters. Further research is necessary to identify the differences in cultural attitudes that may have contributed to these findings.

Aged↗

Selective serotonin reuptake inhibitor discontinuation symptoms.

This paper reviews the literature on selective serotonin reuptake inhibitor discontinuation symptoms. These symptoms have been well described in numerous anecdotal case reports and reports of small series of cases in the Caucasian population. There are no reports in the literature of it occurring in Asian patients. A study involving 65 patients on this type of antidepressant revealed that Asian patients do experience these withdrawal symptoms as well. Seven patients (3 on fluoxetine, 4 on fluvoxamine) reported symptoms similar to those reported by Caucasian patients in the literature. Three of the cases are reported in detail to highlight the clinical presentation in such cases.

Adult↗

Covalent heparin cofactor II-heparin and heparin cofactor II-dermatan sulfate complexes. Characterization of novel anticoagulants.

Heparin cofactor II is a naturally occurring anticoagulant that acts by specifically inhibiting thrombin and is facilitated by the binding of glycosaminoglycans such as heparin and dermatan sulfate. In vivo, heparin cofactor II-glycosaminoglycan complexes dissociate, leaving the inhibitor less active in its ability to function as a component of the anticoagulation pathway. We have produced permanently activated heparin cofactor II molecules by covalent linkage to either heparin or dermatan sulfate. Covalent heparin cofactor II-heparin and heparin cofactor II-dermatan sulfate complexes had catalytic antithrombin activities similar to those of the corresponding starting heparin and dermatan sulfate (86% and 110% of standard heparin and dermatan sulfate activity, respectively). Both heparin cofactor II-heparin and heparin cofactor II-dermatan sulfate had fast bimolecular rate constants of 1.4 x 10(7) M-1 s-1 and 1.3 x 10(7) M-1 s-1, respectively, for reaction with thrombin. The intravenous half-life of the covalent complexes in rabbits was significantly longer than that of free heparin or dermatan sulfate (4.4, 3.4, 0.33, and 0.50 h for heparin cofactor II-heparin, heparin cofactor II-dermatan sulfate, heparin, and dermatan sulfate, respectively). Given their unique properties, these conjugates may have a clinical application for long term, selective inhibition of thrombin.

Animals↗