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Biomedical subjects

Y S Yu

Publications and source records attributed to Y S Yu.

At least 37 records · Page 2Linked to original sources

Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex.

Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine thromboplastin-based PT assays. Taken together, our results suggest that mutations at Gly-48 altered the interaction of factor IX with its extrinsic pathway activator (VIIa-TF complex), its macromolecular substrate (factor X), and its cofactor (factor VIIIa).

Animals↗

The developmental fate of green fluorescent mouse embryonic germ cells in chimeric embryos.

Primordial germ cells (PGCs), as precursors of mammalian germ lineage, have been gaining more attention as a new resource of pluripotent stem cells, which bring a great possibility to study developmental events of germ cell in vitro and at animal level. EG4 cells derived from 10.5 days post coitum (dpc) PGCs of 129/svJ strain mouse were established and maintained in an undifferentiated state. With an attempt to study the differentiation capability of EG4 cells with a reporter protein: green fluorescence protein, and the possible application of EG4 cells in the research of germ cell development, we have generated several EG4-GFP cell lines expressing enhanced green fluorescence protein (EGFP) and still maintaining typical characteristics of pluripotent stem cells. Then, the differentiation of EG4-GFP cells in vitro as well as their developmental fate in chimeric embryos which were produced by aggregating EG4-GFP cells to 8-cell stage embryos were studied. The results showed that EG4 cells carrying green fluorescence have a potential use in the research of germ cell development and other related studies.

Animals↗

Surgical treatment of subretinal neovascular membrane.

The visual results of laser photocoagulation for subfoveal choroidal neovascular membrane (CNVM) has not always been satisfactory. The surgical removal of the neovascular membrane may be another treatment option. To investigate the prognosis and risk factors of this surgery, we analyzed the results of surgical removal of subfoveal CNVM (23 eyes), subfoveal hemorrhage with CNVM (6 eyes), and subfoveal hemorrhage alone (6 eyes). The mean follow-up period was 17.7 months (range 2 to 47 months). The mean preoperative membrane size was 0.89 disc diameter and the mean postoperative retinal pigment epithelial (RPE) defect size was 1.33 disc diameter. Visual improvement was observed in 13 out of the 23 eyes (56.5%) with sufoveal CNVM, four out of the six eyes (66.6%) with subretinal hemorrhage and CNVM, and five out of the six eyes (83.3%) with subretinal hemorrhage only. The visual outcome of subfoveal CNVM surgery was related to the presence of a subfoveal RPE defect (p = 0.005) rather than to the size of the RPE defect. No recurrence of neovascular membrane was observed during the follow up period. In conclusion, surgical removal may be a good alternative treatment for subfoveal CNVM.

Choroidal Neovascularization↗

Scleral perforation after scleral buckling surgery for retinopathy of prematurity.

Scleral perforation occurred as a result of using a silicone band during scleral buckling surgery for subtotal retinal detachment in retinopathy of prematurity (ROP). The patient was initially treated by cryotherapy and scleral buckling surgery for ROP, and was later referred due to a dark bluish mass in the superotemporal quadrant of the eyeball. After removing the overlying whitish membrane, uveal tissue prolapsed through the melted scleral wound (5 mm x 5 mm). A silicone encircling band had passed through the wound and was exposed subconjunctivally around the temporal and the inferior limbus. The band was removed and a scleral allograft was performed. After three years, follow up revealed the eyeball was slightly microphthalmic. Though scleral bucking surgery is helpful for the treatment of advanced ROP, a scleral perforation may develop as a disastrous complication.

Female↗

[Experimental study of incompetency of deep vein of lower limb].

OBJECTIVE: The purpose of this study was to find the best material for valvular wrapping operation of deep vein of lower limb and to study the diagnostic value of colored Ultrasonic-Doppler for valvular incompetency of the deep vein and the function of the popliteal valve. METHODS: Strips of autogenous saphenous vein, autogenous fascia lata and pieces of polytetrafluroethylene artificial vessel were used respectively as the wrapping material for narrowing the valve in 30 dogs. The results of three different wrapping material were obtained by colored Ultrasonic-Doppler and transpopliteal venography in 78 patients. The hemokinetics of the popliteal valve was examined in 20 normal persons. RESULTS: In the saphenous vein and fascia lata groups, diffuse fibrosis and marked narrowing of the femoral vein were found, while in the group of artificial vein graft, the graft was intact without prominent fibrosis and narrowing of the vein. In comparing with the result of venography, the accuracy of diagnosis by colored Ultrasonic-Doppler was 91.86%. The femoral and popliteal venous valves closed at the same time when holding the breath, but the popliteal venous valve opened more widely than the femoral venous valve when the calf muscles of the leg contracted. CONCLUSION: It was suggested that the graft was the best material for valvular wrapping operation, and colored Ultrasonic-Doppler was an important and non-invasive method for the diagnosis of incompetency of deep vein. The popliteal venous valve was the important barrier for protection of the function of deep vein.

Animals↗

Transmembrane-domain trapping: a novel method for isolation of cDNAs encoding putative membrane proteins.

We have developed a method that enables us to isolate cDNAs of putative membrane proteins. The system is designed to isolate a cDNA which can provide the transmembrane domain to the extracellular part of the IL-2 receptor alpha chain. We constructed a p18Mac vector by putting part of the IL-2 receptor alpha chain cDNA that encoded its signal sequence and extracellular domain, a cDNA cloning site and a poly(A) additional signal after a strong promoter SRalpha. If a cloned cDNA provides a transmembrane domain in-frame, the extracellular domain of the IL-2 receptor alpha chain will be expressed on the surface of the transfected cells. Otherwise, the chimeric protein will be either secreted or retained inside the transfected cells. We made a cDNA library using p18Mac and screened for cDNA clones which allowed the expression of the extracellular domain of the IL-2 receptor alpha chain on the cell surface. Of the 2000 clones screened, 5 clones were scored as positive. Partial sequence analysis revealed that one clone encoded the amyloid precursor protein, two others encoded mitochondrial proteins and the rest were new. These results suggest the system is effective in isolating cDNAs encoding putative membrane proteins.

Amino Acid Sequence↗

Anatomical and visual results of vitreous surgery for advanced retinopathy of prematurity.

We studied the visual acuity and anatomical stability of 101 eyes which had undergone vitreous surgery for advanced retinopathy of prematurity. All were followed up for at least six months. The anatomical and visual results of vitrectomy in 87 eyes were reviewed. The patients' average age at surgery was 9.6 months, and the average follow-up period was 37.6 months. To preserve the structure of the eyeball or to prevent further complications due to a shallow anterior chamber, a further 14 eyes underwent lensectomy. Total attachment was achieved in 20 eyes(23.0%), and partial attachment in 24(27.6%). Finally, 42 eyes(48.3%) were able to perceive light, while fixation and following occurred in 15(17.2%). Six eyes(6.9%) were able to identify form. The relatively useful vision achieved in cases of advanced retinopathy of prematurity in this study with long follow-up suggests that the rationale of vitreous surgery is to salvage functional retina and to prevent total blindness and other complications.

Child↗

Retinopathy of prematurity-mimicking retinopathy in full-term babies.

The purpose of this study was to analyze the fundus findings and associated abnormalities in full-term babies with retinopathy of prematurity (ROP)-mimicking retinopathy. In twenty-seven such babies suffering from this condition, retinal findings were retrospectively analyzed. These babies were not premature and had not required supplementary oxygen; there was no family history of the disease, and no known causes. Bilaterality and severity of retinopathy were compared between groups with associated systemic abnormalities and those without. Forty eyes in twenty-seven full-term babies had abnormal retinal findings; dragged retina accounted for 42.5%, and falciform retinal fold for 47.5%, and retrolental membrane for 10%. Nine babies had associated brain abnormalities, and in these, severe bilateral retinopathy was more likely to occur than in those without abnormalities. These results suggest that if full-term babies have associated abnormalities of the brain, the presence of retinopathy should be ascertained postnatally by cautious examination of the retina.

Brain Diseases↗

Interleukin-1 receptor antagonist allele: is it a genetic link between Henoch-Schönlein nephritis and IgA nephropathy?

Henoch-Schönlein purpura nephritis (HSPN) is a multi-organ systemic vasculitis, which shares many clinical, histological and immunological features with IgA nephropathy (IgAN). To address whether these two diseases have a common genetic background, the polymorphism of the variable number tandem repeat (VNTR) of IL-1 receptor antagonist (IL-1ra) gene has been analyzed using PCR in patients diagnosed with HSPN (N = 43) and IgAN (N = 97), together with normal controls (N = 98) and patients with acute post-infectious glomerulonephritis (APGN), under the concept that IL-1 might play an important role in mediating pathogenesis of vasculitis and glomerulonephritis. It was found that the allele frequency and carriage rate of the interleukin-1 receptor antagonist allele (IL1RN*2) of the IL-1ra gene increased significantly in HSPN patients as compared to IgAN (P < 0.01), APGN (P < 0.05) and normal subjects (P < 0.01). Interestingly, varied carriage rates of IL1RN*2 were found among various groups of IgAN patients presenting with different clinical manifestations. The carriage rate of IL1RN*2 was significantly higher in patients with recurrent gross hematuria than other groups of IgAN patients (P < 0.01). Furthermore, although the carriage rate of IL1RN*2 was higher in HSPN (46.5%) than average IgAN patients (26.8%; P < 0.01), there was no significant difference in the carriage rate of IL1RN*2 between HSPN and those IgAN patients with recurrent gross hematuria (42.8%l P > 0.05). It suggested that the IL1RN*2 allele might be a genetic marker shared by HSPN and a special group of IgAN patients with recurrent gross hematuria. Our preliminary observation provided a genetic evidence to support the hypothesis that HSPN and certain subgroup of IgAN are closely related diseases. Such an association of the gene polymorphism of IL-1ra between HSPN and IgAN with recurrent gross hematuria might serve as a key to explore their pathogenesis and eventually a specific intervention.

Adolescent↗

Persistent hyperplastic primary vitreous in male twins.

Persistent hyperplastic primary vitreous (PHPV) occurs sporadically and few familial occurrences have been reported. The authors report PHPV unassociated with other congenital anomalies in male twins. One underwent a lensectomy for the management of angle-closure glaucoma and the other was treated for amblyopia. These cases provide further evidence to suggest autosomal recessive inheritance, though the possibility of developmental error cannot be excluded.

Amblyopia↗

Improvements in visual acuity following limbal lensectomy for subluxated lenses in children.

BACKGROUND AND OBJECTIVE: To report the surgical results of limbal lensectomy using an automated vitrectomy instrument for the treatment of subluxated lenses in children. PATIENTS AND METHODS: The authors reviewed the charts of children who underwent surgery for subluxated lenses. Limbal lensectomies with an "in the bag" technique were performed on 18 eyes of 10 patients. The indications for surgery were a best-corrected visual acuity of less than 20/60, bisection of pupil by the lens, or both. RESULTS: Best-corrected visual acuity improved in all 18 eyes (paired t test, P < .01). In 1 eye, transient anterior chamber hyphema occurred during the early postoperative period. No other significant complications were found during an average follow-up of 19.6 months. CONCLUSION: Limbal lensectomy for subluxated lenses in children improved visual acuity without severe complications.

Adolescent↗

The promoter structure of TGF-beta type II receptor revealed by "oligo-capping" method and deletion analysis.

The promoter of TGF-beta type II receptor lacks TATA box or CAAT box. In order to define the exact transcriptional start site(s), we used "oligo-capping" method developed by ourselves. The major transcripts were started from GAA located between -35 and -33 relative to 5' end of cDNA. Other minor transcripts started from -4, +11 and +17. Deletion analysis of this promoter region revealed that it contained two adjacently located promoters (P1 and P2) capable of acting by itself. The P1 is located between -22 and +55 which covers the minor transcriptional start sites described above. The P2 is located just upstream of the P1 between -137 and -22. The results showed all of the transcripts were started either from P1 or P2.

Animals↗

Surgical management for persistent pupillary membrane with vitreous scissors.

Persistent pupillary membranes are common congenital disorders. To reduce the surgical complications, we used vitreous scissors instead of conventionally used Vannas scissors to remove the membrane and reviewed the surgical results. Five eyes of 4 children with persistent pupillary membrane were treated by surgery. Through the 1.5 mm limbal incision, the membrane was removed by using vitreous scissors after intracameral sodium hyaluronate. After 22.6 months follow-up, all pupils of operated eyes were round and no complications associated with the surgery were found. Three eyes showed improved visual acuities after the operation. We suggest that the surgery with vitreous scissors is better than with Vannas scissors.

Anterior Chamber↗

The outcome of cryotherapy for retinopathy of prematurity (ROP) according to ROP location.

Cryotherapy has been shown to be an effective treatment for retinopathy of prematurity (ROP) stage 3+. However, the outcome of cryotherapy is less favorable in zone 1 ROP than in zone 2 ROP. We suspected whether there may be differences in the outcomes of cryotherapy if the zone of ROP is further divided. So we reviewed the records of 85 premature infants (145 eyes) who had undergone cryotherapy for ROP. The frequencies of favorable outcome were 42.9% of 14 eyes (zone 1), 78.9% of 38 eyes (posterior zone 2), 92.9% of 70 eyes (mid zone 2), and 100.0% of 23 eyes (anterior zone 2), respectively (p < 0.001). These results suggest that the more posteriorly the ROP is located, the less favorable the outcome of cryotherapy.

Cryotherapy↗

Change of refraction in premature infants after cryotherapy for retinopathy of prematurity between the age of six months and three years.

To investigate the chronological change of refraction in premature infants after cryotherapy for retinopathy of prematurity (ROP), cycloplegic refractions had been performed at 6 months and 3 years after term in premature infants who underwent cryotherapy for ROP. The changes of refractions between the two study ages were evaluated not only in the total cryo-treated eyes, but also in the subdivided groups according to the posterior pole appearances. In the total 61 eyes of 32 premature infants, mean spherical equivalents were -4.05D vs. -5.94D (6 months vs. 3 years) (p = 0.0001). In the normal posterior pole group (48 eyes), mean spherical equivalents were -3.45D vs. -5.68D (6 months vs. 3 years) (p = 0.0000), and in the abnormal posterior pole group (13 eyes), -6.28D vs. -6.86D (6 months vs. 3 years) (p = 0.6496). These results mean that there is a myopic progressive change between 6 months and 3 years after term in the cryo-treated eyes for acute ROP and it is more evident in the eyes with normal posterior pole.

Acute Disease↗

Surgical management for stage 5 retinopathy of prematurity.

To determine the prognosis of advanced retinopathy of prematurity (ROP) after surgery, we reviewed retrospectively the results of vitrectomy performed between November 1987 and December 1993 in 38 eyes with stage 5 ROP. The patients' mean age at surgery was 11 months, mean follow-up period was 24.1 months. Anatomical success, defined as reattachment of posterior pole retina, was achieved in 11 eyes (29.0%) and functional success, defined as presence of fixation and following was achieved in 7 eyes (18.4%). Anatomical success was well correlated with preoperative configuration of retina, i.e. open-funnel type showed better results than closed-funnel type (44.4% compared to 15.0%). There were no differences between anatomical success and failure group according to gestational age, birth weight, age at the time of diagnosis of ROP, chronological and postconceptional age, and body weight at the time of surgery. For good prognosis, it is necessary to operate early in stage 5 ROP when retinal funnel is still open.

Child, Preschool↗

Photosensitization-induced retinopathy in the newborn beagle.

PURPOSE: Photosensitization is a mechanism by which oxygen and light may interact to generate free radicals capable of tissue injury. It has been proposed as a possible etiologic mechanism in the development of retinopathy of prematurity. The authors report the effects of light exposure and a photosensitizer, rose bengal (RB), on the developing retina of the beagle puppy. METHODS: Seven purebred beagle puppies (2 or 7 days old) were given RB (7.5 mg/ml) intravenously (0.9 ml bolus followed by a 74 microliters/min constant infusion), and one eye was exposed to filtered light delivered by a modified slit lamp at 30 mW/cm2 for 5, 15, 25, 35, and 45 minutes. The fellow eye was not irradiated and served as an RB-only control. Three beagles were exposed to light (one eye only) for 15 to 120 minutes in the absence of RB to provide light-only and no-treatment control eyes. Animals were followed clinically by indirect ophthalmoscopy and fluorescein angiography, and eyes were processed for light microscopy. RESULTS: Clinical and/or histologic abnormalities were found in all seven eyes exposed to light in the presence of rose bengal, as follows: vitreous hemorrhage in four eyes, incomplete peripheral retinal vascularization in four eyes, fibrovascular/fibrocellular proliferation with traction on the retina in two eyes (including preretinal neovascularization in one eye), total or partial retinal detachment in two eyes, dilated peripheral vessels compatible with shunt vessels in one eye, retinal dysplasia with loss of normal architecture and formation of rosettes in five eyes. All 13 control eyes showed normal, complete retinal vascularization. CONCLUSIONS: The failure to progress to the end-stage tractional retinal detachment seen in human infants is a shortcoming of existing animal models. Photosensitization injury to the developing retina in this animal model can produce a spectrum of retinal pathology that includes extraretinal vascularization and subsequent retinal detachment.

Animals↗