Expression pattern of high-affinity tyrosine kinase Aduring the development of human fetal spinal cord.

High-affinity tyrosine kinase A (TrkA) is responsible for the biological activities of nerve growth factor. Most studies of the molecular mechanisms of TrkA that underlie the development of the spinal cord have been conducted in animals and the expression pattern of TrkA during the development of the human fetal spinal cord is not well characterized. We investigated 45 3-28-week-old (G3W-G28W) human fetuses. We assessed the expression pattern of TrkA in the human fetal spinal cord using immunohistochemistry, western blot and reverse transcription polymerase chain reaction to clarify the spatiotemporal developmental changes and to determine the role TrkA plays in development. TrkA immunoreactive products were detected widely in the alar and basal plates, ependyma, glial cells, gray and white matter, internal limiting membrane, mantle layer, marginal layer, neuroepithelium and neurons during this period of development. Expression levels of TrkA mRNA and protein peaked at G12W and G16W, respectively. The strong expression of TrkA was closely related to the formation of the dorsal and ventral horns, and the differentiation of somatic motor neurons during late embryonic development. Our findings suggest that TrkA receptors play crucial roles during the development of human fetal spinal cord. The characteristic expression patterns may clarify the developmental characteristics of the human spinal cord.

Endovenous laser ablation: mechanism of action.

OBJECTIVES: The objective of this study is to review the basics of laser and established tissue response patterns to thermal injury, with specific reference to endovenous laser ablation (EVLA). This study also reviews the current theories and supporting aspects for the mechanism of action of EVLA in the treatment of superficial venous reflux. METHODS: The method involves the review of published literature and original investigation of histological effects of 810 nm and 980 nm wavelength EVLA on explanted blood-filled bovine saphenous vein in an in vitro system. RESULTS: The existing histological reports confirm that EVLA produces a transmural vein wall injury, typically associated with perforations and carbonization. The pattern of injury is eccentrically distributed, with maximum injury occurring along the path of laser contact. Intravenous temperature monitoring studies during EVLA have confirmed that the peak temperatures at the fibre tip exceed 1000 degrees C, and continuous temperatures of at least 300 degrees C are maintained in the firing zone for the majority of the procedure. Steam production during EVLA, which occurs early in the photothermolytic process when temperatures reach 100 degrees C, accounts for only 2% of applied energy dose, and is therefore unlikely to be the primary mechanism of action of thermal injury during the procedure. CONCLUSION: EVLA causes permanent vein closure through a high-temperature photothermolytic process at the point of contact between the vein and the laser.

Inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion.

PURPOSE: To describe the pathophysiology, identification and management of inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion has been reported. REVIEW FINDINGS: These aneurysms are thought to arise due to increased flow through the pancreaticoduodenal arcades. The arcades first enlarge, and then form focal aneurysms which may rupture. The aneurysms can be treated through endovascular techniques or by surgery, though the former is a preferred approach.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.