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Biomedical subjects

C M Fan

Publications and source records attributed to C M Fan.

At least 19 recordsLinked to original sources

Review of first year result of photodynamic therapy on age-related macular degeneration in Chinese population.

PURPOSE: To evaluate the effect of verteporfin therapy (Visudyne) on age-related macular degeneration (AMD) in Chinese patients. The baseline characteristic and the visual outcome will be compared with the treatment of AMD with photodynamic therapy study (TAP) and verteporfin in photodynamic therapy study (VIP). DESIGN: Retrospective comparative case series. METHOD: We recruited patients >50 years old, with best-corrected visual acuity >20/200 and fluorescein angiography documenting subfoveal either predominantly classic with greatest linear dimension <5400 mum or pure occult choroidal neovascularization (CNV) secondary to AMD. We applied non-thermal laser to the lesion 15 min after visudyne infusion as described in TAP study. Patients were followed up with fluorescein angiography every 3 months. Additional treatment would be offered if there was evidence of recurrence of CNV. OUTCOME MEASURE: Baseline characteristic and visual outcome. RESULT: In all, 46 eyes of 42 patients were enrolled at our centre from July 2002 to June 2003. They comprised 11 eyes with predominantly classic lesions and 35 eyes with pure occult lesion. The mean number of treatment sessions given was 2.9 in the first year. At the 12-month examination, there were 63 and 29% of patients showing visual improvement in predominantly classic and occult groups, respectively, while there were only 16% of patients in the TAP study and 12% of patients in the VIP study showing visual improvement in the same period. CONCLUSION: Verteporfin therapy for subfoveal CNV is beneficial to Chinese patients with AMD at first year. The visual result seems to be better than that observed in Caucasian patients.

Aged↗

Photoelectrocatalytic degradation of humic acid in aqueous solution using a Ti/TiO2 mesh photoelectrode.

Humic acid (HA) is one of natural organics existing in water supply as a precursor of trihalomethanes formation in chlorination. The photo-degradation of HA in aqueous solution by photoelectrocatalytic (PEC) oxidation using a Ti/TiO2 mesh electrode was investigated in terms of UV absorbance at 254 nm, colour and TOC concentration. The key factors affecting the PEC oxidation efficiency were studied, including the concentration of electrolyte, electrical bias applied. pH value of HA solution, the intensity of incident light and the area of Ti/TiO2 mesh photoelectrodes. The first-order kinetic model was applied to describe the PEC oxidation, in which the kinetic constant k was verified by the experimental data as a function of the concentration of electrolyte, light intensity, the area of Ti/TiO2 mesh electrode and the voltage of electrical bias applied. It was found that there was an optimal bias voltage of 1.63 V and low pH value was favourable for TOC removal in HA solution. Our investigation showed that PEC oxidation was a convenient way to mineralise the organic matters with high efficiency.

Coloring Agents↗

Enhancement of photocatalytic oxidation of humic acid in TiO2 suspensions by increasing cation strength.

This study aimed at improving the photocatalytic (PC) oxidation of humic acids (HA) in TiO2 suspensions by adding cationic ion such as calcium or magnesium. A set of tests was first conducted in the dark to study the adsorption of HA onto TiO2 in suspensions at different pH and calcium concentrations. The experiment demonstrated that the adsorption of HA onto the TiO2 particles was either pH-dependent or calcium strength-dependent due to electrostatic interaction and calcium ion bridging. The photodegradation of HA in the presence of UV irradiation was investigated as a function of pH and the concentration of calcium and magnesium ions. The results showed that the adsorption behavior between HA and TiO2 played a very important role during the PC oxidation process. The PC oxidation could be enhanced at neutral pH by increasing the cation strength. The kinetics of HA PC degradation in TiO2 suspensions with different initial concentrations was also studied using the Langmuir-Hinshelwood model.

Catalysis↗

Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite.

The dorsal-ventral polarity of the somite is controlled by antagonistic signals from the dorsal neural tube/surface ectoderm, mediated by WNTs, and from the ventral notochord, mediated by sonic hedgehog (SHH). Each factor can act over a distance greater than a somite diameter in vitro, suggesting they must limit each other's actions within their own patterning domains in vivo. We show here that the growth-arrest specific gene 1 (Gas1), which is expressed in the dorsal somite, is induced by WNTs and encodes a protein that can bind to SHH. Furthermore, ectopic expression of Gas1 in presomitic cells attenuates the response of these cells to SHH in vitro. Taken together, these data suggest that GAS1 functions to reduce the availability of active SHH within the dorsal somite.

Animals↗

Growth arrest specific gene 1 is a positive growth regulator for the cerebellum.

Postnatal cerebellum development involves the generation of granule cells and Bergmann glias (BGs). The granule cell precursors are located in the external germinal layer (EGL) and the BG precursors are located in the Purkinje layer (PL). BGs extend their glial fibers into the EGL and facilitate granule cells' inward migration to their final location. Growth arrest specific gene 1 (Gas1) has been implicated in inhibiting cell-cycle progression in cell culture studies (G. Del Sal et al., 1992, Cell 70, 595--607). However, its growth regulatory function in the CNS has not been described. To investigate its role in cerebellar growth, we analyzed the Gas1 mutant mice. At birth, wild-type and mutant mice have cerebella of similar size; however, mature mutant cerebella are less than half the size of wild-type cerebella. Molecular and cellular examinations indicate that Gas1 mutant cerebella have a reduced number of granule cells and BG fibers. We provide direct evidence that Gas1 is required for normal levels of proliferation in the EGL and the PL, but not for their differentiation. Furthermore, we show that Gas1 is specifically and coordinately expressed in both the EGL and the BGs postnatally. These results support Gas1 as a common genetic component in coordinating EGL cell and BG cell proliferation, a link which has not been previously appreciated.

Animals↗

Transdifferentiation of the ventral retinal pigmented epithelium to neural retina in the growth arrest specific gene 1 mutant.

During eye development, retinal pigmented epithelium (RPE) and neural retina (NR) arise from a common origin, the optic vesicle. One of the early distinctions of RPE from NR is the reduced mitotic activity of the RPE. Growth arrest specific gene 1 (Gas1) has been documented to inhibit cell cycle progression in vitro (G. Del Sal et al., 1992, Cell 70, 595--607). We show here that the expression pattern of Gas1 in the eye supports its negative role in RPE proliferation. To test this hypothesis, we generated a mouse carrying a targeted mutation in the Gas1 locus. Gas1 mutant mice have microphthalmia. Histological examination revealed that the remnant mutant eyes are ingressed from the surface with minimal RPE and lens, and disorganized eyelid, cornea, and NR. Analysis of the Gas1 mutant indicates that there is overproliferation of the outer layer of optic cup (E10.5) immediately after the initial specification of the RPE. This defect is specific to the ventral region of the RPE. Using molecular markers for RPE (Mi and Tyrp2) and NR (Math5), we demonstrate that there is a gradual loss of Mi and Tyrp2 expression and an appearance of Math5 expression in the mutant ventral RPE region, indicating that this domain becomes respecified to NR. This "ectopic" NR develops as a mirror image of the normal NR and is entirely of ventral identity. Our data not only support Gas1's function in regulating cell proliferation, but also uncover an unexpected regional-specific cell fate change associated with dysregulated growth. Furthermore, we provide evidence that the dorsal and ventral RPEs are maintained by distinct genetic components.

3T3 Cells↗

Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus.

The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show here that Sim1 heterozygous mice are viable but develop early-onset obesity, with increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are hyperphagic but their energy expenditure is not decreased, distinguishing them from other mouse models of early-onset obesity such as deficiencies in leptin and melanocortin receptor 4. Quantitative histological comparison with normal littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer cells without a selective loss of any identifiable major cell type. Since acquired lesions in the PVN also induce increased appetite without a decrease in energy expenditure, we propose that abnormalities of PVN development cause the obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1. Pathways controlling the development of the PVN thus have the potential to cause obesity in both mice and humans.

Adipose Tissue↗

Regression of perianeurysmal fibrosis and ureteral dilation following endovascular repair of inflammatory abdominal aortic aneurysm.

An inflammatory component to abdominal aortic aneurysms (AAA) is thought to occur in approximately 5% of cases. Accompanying ureteral entrapment may be involved in 20% of these. Transabdominal repair of inflammatory AAA with ureterolysis may result in increased complications. Many authorities have recommended a retroperitoneal approach to decrease dissection. Similarly, an endovascular approach has been utilized. We report here the results of a patient with an inflammatory AAA with bilateral ureteral obstruction successfully treated with endovascular stent graft repair and bilateral ureteral stents with exclusion of the aneurysm and resolution of hydronephrosis.

Aged↗

Embryonic expression patterns of the mouse and chick Gas1 genes.

Control of cell proliferation is essential to generate the defined form of a multi-cellular organism. While much is known about the regulators for cell cycle progression, relatively little is known about the state of growth arrest. Growth arrest (G0) is defined as a cell in a metabolically active but proliferation-quiescent state (reviewed in Baserga (1985) The Biology of Cell Reproduction), typically induced by serum starvation in vitro. Using subtractive hybridization, Schneider et al. (Cell 54 (1988) 787) identified six genes (Gas1 through Gas6) whose expressions are upregulated in serum-deprived NIH3T3 cells. Among the Gas genes, Gas1 is the only one that can cause growth arrest when expressed in cultured cell (Cell 70 (1995) 595; Int. J. Cancer 9 (1998) 569). Here, we describe for the first time the expression pattern of Gas1 during mouse embryogenesis. Our data reveal that Gas1 is expressed in many regions that the cells are actively proliferating and suggest that it may have other roles during development than negatively regulating cell proliferation. Furthermore, we have cloned the chick GAS1 gene and documented the similarity and divergence of Gas1 gene expression patterns between the two species.

Amino Acid Sequence↗

Endovascular stent-graft in abdominal aortic aneurysms: the relationship between patent vessels that arise from the aneurysmal sac and early endoleak.

PURPOSE: To determine the association of patent sac branch vessels (lumbar and inferior mesenteric arteries [IMAs]) with early endoleak rate after stent-graft repair of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: Pre- and postoperative computed tomographic (CT) angiograms in 158 patients who underwent stent-graft AAA repair were retrospectively reviewed to determine the preoperative patency of IMAs and other sac branch vessels (feeders) and presence or absence of immediate postoperative endoleak. Relationships of early endoleak rate with total branch vessel, IMA, and lumbar artery patency and graft type were evaluated. RESULTS: There was a significant association between patency of sac feeders and rate of early endoleak, especially type 2. As total patent feeders increased from zero to three to four to six, total endoleak rate increased from 6% (one of 17) to 35% (30 of 86); type 2 endoleak rate, from 0% to 25%. IMA patency was significantly associated with total early endoleak rate. Increasing lumbar artery patency also was associated with significantly higher total and type 2 endoleak rates: With zero to three lumbar arteries, the total endoleak rate was 17% and type 2 endoleak rate was 13%, as compared with 60% and 50%, respectively, with more than six patent lumbar arteries. CONCLUSION: Sac branch vessel patency is associated with significantly higher early total and type 2 endoleak rates after stent-graft repair of AAAs; thus, patent sac branches play an important role in the pathogenesis of endoleaks.

Aged↗

ARNT2 acts as the dimerization partner of SIM1 for the development of the hypothalamus.

One major function of the hypothalamus is to maintain homeostasis by modulating the secretion of pituitary hormones. The paraventricular (PVN) and supraoptic (SON) nuclei are major integration centers for the output of the hypothalamus to the pituitary. The bHLH-PAS transcription factor SIM1 is crucial for the development of several neuroendocrine lineages within the PVN and SON. bHLH-PAS proteins require heterodimerization for their function. ARNT, ARNT2, and BMAL1 are the three known general heterodimerization partners for bHLH-PAS proteins. Here, we provide evidence that Sim1 and Arnt2 form dimers in vitro, that they are co-expressed in the PVN and SON, and that their loss of function affects the development of the same sets of neuroendocrine cell types within the PVN and SON. Together, these results implicate ARNT2 as the in vivo dimerization partner of SIM1 in controlling the development of these neuroendocrine lineages.

ARNTL Transcription Factors↗

Clinical outcome of internal iliac artery occlusions during endovascular treatment of aortoiliac aneurysmal diseases.

PURPOSE: To determine the clinical outcome of hypogastric artery occlusion in patients who underwent endovascular treatment of aortoiliac aneurysmal disease. MATERIAL AND METHODS: From January 1994 to March 1998, 94 patients underwent endovascular treatment of aneurysmal diseases involving the infra-abdominal aorta or iliac arteries. Preoperative and intraoperative radiologic data were reviewed. Discharge summaries, clinic visits, and phone calls formed the basis for clinical follow-up, with a mean follow-up period of 7.3 months (range, 1-24 months). RESULTS: Because of the anatomy of the aneurysms, 28 patients required occlusion of one or more hypogastric arteries. One of the 28 patients died of unrelated causes before follow-up. Seven (26%) of the remaining 27 patients developed symptoms attributable to the hypogastric artery occlusions. Five patients developed new buttock or thigh claudication; of these five patients, three with initially mild symptoms noted complete or near complete resolution of symptoms upon follow-up. One patient with originally significant claudication at 2-year follow-up noted near resolution of symptoms. The other patient with severe pain did not improve significantly on final 1-year follow-up before his death (of unrelated causes). Other clinical complications were worsening sexual function in one patient and a nonhealing sacral decubitus ulcer that developed in a debilitated patient in the postoperative setting, which required surgery. No bowel ischemia was observed. CONCLUSION: When treating aortoiliac aneurysmal disease through an endovascular approach, the occlusion of internal iliac artery is often necessary but carries with it a small but finite chance of morbidity.

Adult↗

Utility and reliability of endovascular aortouniiliac with femorofemoral crossover graft for aortoiliac aneurysmal disease.

OBJECTIVE: The purpose of this study was to determine the early efficacy of endovascular aortouniiliac stent grafts with femorofemoral bypass graft in the treatment of aortoiliac aneurysmal disease. METHODS: We analyzed 51 consecutive patients from January 1997 to March 1999 with a mean follow-up of 15.8 months. Patients ranged in age from 44 to 93 years (mean, 75 years) with a mean aortic aneurysm diameter of 6.2 cm. Technical success was achieved in 50 patients; one patient required conversion to open repair intraoperatively. We placed 28 custom-made and 22 commercial devices. The mean operative time was 223 minutes. The endograft was extended to the external iliac artery in 42% of cases. The contralateral common iliac artery was occluded using either a closed covered stent or intraluminal coils. RESULTS: The median hospital stay was 4 days with an average intensive care unit stay of 0.25 days. There were no operative mortalities. Two patients died during follow-up from unrelated conditions. Endoleaks occurred in 11 patients (22%); seven patients (14%) required intervention (four catheter based, three operative). Other complications occurred in 38% of patients but were largely remote or wound related. One femorofemoral bypass graft occluded immediately postoperatively as a result of an intraprocedural external iliac dissection yielding a 98% primary patency and 100% secondary patency. Clinical success was achieved in 88% of patients. CONCLUSIONS: These data suggest that this strategy represents a reliable method of repair of aortoiliac aneurysmal disease and extends the capability of an endoluminal approach to patients with complex iliac anatomy.

Adult↗

Inferior vena caval filters: review of a 26-year single-center clinical experience.

PURPOSE: To review a 26-year single-center clinical experience with inferior vena caval filters. MATERIALS AND METHODS: During 1973-1998, 1,765 filters were implanted in 1,731 patients. Hospital files were reviewed, and data were collected about the indications, safety, effectiveness, numbers, and types of caval filters. Fatal post-filter pulmonary embolism (PE) was considered the primary outcome. Morbidity and mortality were determined as secondary outcomes. Survival and morbidity-free survival curves were calculated. RESULTS: The prevalence of observed post-filter PE was 5.6%. It was fatal in 3.7% of patients. In most patients, fatal PE occurred soon after filter insertion (median, 4.0 days; 95% CI: 2.2, 5.8 days). Major complications occurred in 0.3% of procedures. The prevalence of observed post-filter caval thrombosis was 2.7%. The 30-day mortality rate was 17.0% overall, higher among patients with neoplasms (19.5%) as compared with those without neoplasms (14.3%; P =.004). Filter efficacy and associated morbidity were not different in 46 patients with suprarenal filters. The rate of filters placed for prophylaxis was 4.7% overall and increased to 16.4% in 1998. From 1980 to 1996, there was a fivefold increase in the number of caval filter implants. In recent years, more filters were implanted in younger patients. CONCLUSION: Inferior vena caval filters provide protection from life-threatening PE, with minimal morbidity.

Adolescent↗

SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm.

Dorsoventral polarity of the somitic mesoderm is established by competitive signals originating from adjacent tissues. The ventrally located notochord provides the ventralizing signals to specify the sclerotome, while the dorsally located surface ectoderm and dorsal neural tube provide the dorsalizing signals to specify the dermomyotome. Noggin and SHH-N have been implicated as the ventralizing signals produced by the notochord. Members of the WNT family of proteins, on the other hand, have been implicated as the dorsalizing signals derived from the ectoderm and dorsal neural tube. When presomitic explants are confronted with cells secreting SHH-N and WNT1 simultaneously, competition to specify the sclerotome and dermomyotome domains within the naive mesoderm can be observed. Here, using these explant cultures, we provide evidence that SHH-N competes with WNT1, not only by upregulating its own receptor Ptc1, but also by upregulating Sfrp2 (Secreted frizzled-related protein 2), which encodes a potential WNT antagonist. Among the four known Sfrps, Sfrp2 is the only member expressed in the sclerotome and upregulated by SHH-N recombinant protein. We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a. Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm.

3T3 Cells↗

Remembrance of things PAS: regulation of development by bHLH-PAS proteins.

Strange fits of passion I have knownellipsis (W Wordsworth, 'Strange fits of passion'.) bHLH-PAS proteins are regulators of developmental and physiological events that are well conserved between vertebrates and invertebrates. Recent studies using mouse knockouts of bHLH-PAS genes have provided novel insight into the roles of hypoxia inducible factors in controlling oxygen-regulated development and homeostasis, and the role of Single-minded-1 in regulating development and transcription in the hypothalamus. The Drosophila spineless and vertebrate Aryl hydrocarbon receptor bHLH-PAS orthologs both function in chemosensory processes, but in fundamentally different ways. Spineless controls antennal, limb, and sensory cell development, whereas the Aryl hydrocarbon receptor regulates the response to toxin metabolism. Structural analyses of the PAS domain provide insight into how this interaction domain can act as ligand-binding environmental sensor and signal transducer.

Animals↗