Biomedical subjects

D Y Yu

Publications and source records attributed to D Y Yu.

At least 55 records · Page 3Linked to original sources

PubMed1998

Laser-induced chorioretinal venous anastomosis for nonischemic central retinal vein occlusion: evaluation of the complications and their risk factors.

PURPOSE: To evaluate the complications of laser-induced chorioretinal venous anastomosis in nonischemic central retinal vein occlusion (CRVO) and to identify the associated risks. METHODS: A retrospective consecutive series of 91 eyes (91 patients) with nonischemic CRVO with a mean +/- SD duration of 15.0 +/- 15.2 weeks (range, 3 to 72 weeks )and corrected visual acuity reduced to 20/100 or less because of perfused macular edema were reviewed. All eyes had one or more anastomotic attempts using argon laser (combined with Nd-YAG laser in 46 eyes) and a minimum of 12 months of follow-up. RESULTS: Successful chorioretinal venous anastomoses were created in 49 eyes (54%). Eighteen eyes (20%) had neovascular complications. These consisted of intravitreal, intraretinal, and subretinal neovascular membranes and were significantly associated with retinal ischemia (P < .001). There was avascular fibrous tissue proliferation at the anastomotic site in eight eyes (9%), and it was not associated with retinal ischemia (P = .727). No eye developed further capillary nonperfusion once an anastomosis became functional. A chorioretinal venous anastomosis was associated with improved vision (P < .001); 84% of eyes had an average +/- SD improvement of 4.3 +/- 3.8 lines (range, 2 to 20 lines), with the remaining 16% having no improvement or reduced vision. CONCLUSION: The major vision-threatening complication of laser-induced chorioretinal venous anastomosis for nonischemic CRVO is neovascular membranes occurring at the anastomotic site; these are associated with retinal ischemia. Prompt laser photocoagulation to areas of retinal ischemia that develop after the anastomotic attempt has been made may reduce the risk and severity of this complication.

Adult↗

PubMed1998

The distribution of angioarchitectural changes within the vicinity of the arteriovenous crossing in branch retinal vein occlusion.

OBJECTIVE: Branch retinal vein occlusions (BRVOs) are known to occur most commonly in the vicinity of arteriovenous (A/V) crossings. The authors aimed to identify types of venous wall abnormalities in BRVO and document their position in relation to the A/V crossing. DESIGN: A retrospective review of the color photographs and fluorescein angiograms from the most recent 110 patients with first- or second-order BRVO was performed. MAIN OUTCOME MEASURES: The films were examined for the presence of angioarchitectural changes of specified type within one-quarter disk diameter of the A/V crossing involved in the BRVO. The specific changes noted were fluorescein leakage, presumed thrombi, and flow abnormalities, which were recorded along with their position in relation to the A/V crossing. RESULTS: Of the 110 patients diagnosed with BRVO, 59 had photography of satisfactory quality. Forty-one (70%) of these 59 patients had venous lesions, of which significantly more (chi-square -5.74, P < 0.02) were downstream (56%) than upstream (12%) from the A/V crossing. Thirty-two percent were upstream and downstream. Of the hemodynamic changes seen, 49% had late venous phase leakage of fluorescein, 85% had abnormal flow, and 7% had presumed thrombi. All thrombi seen were downstream. CONCLUSIONS: Venous lesions in the vicinity of the A/V crossing commonly are seen in BRVO, most of which occur downstream. This suggests that the venous narrowing at the crossing may induce downstream hemodynamic changes predisposing to endothelial damage and thrombus generation.

Arteriovenous Malformations↗

PubMed1998

Intracellular structures of retinal vascular endothelium in normal and early diabetic rats.

PURPOSE: To determine whether the arrangement of microfilaments in retinal vascular endothelium is altered in early diabetes. METHODS: F-actin and nuclei of retinal vascular endothelial cells of normal and diabetic (28 weeks postinduction) rats were examined using confocal microscopy. RESULTS: An increase in the incidence of aberrant F-actin bundle arrangement in the diabetic retinal arteriole was observed, but there was no disruption of peripheral border F-actin. The diameter of superficial capillaries was increased in diabetic rats. CONCLUSION: These changes may be related to the endothelial dysfunction demonstrated in a previous pharmacological study.

Actins↗

PubMed1998

Preservation of vasoactive properties of human retinal arteries after cryopreservation.

PURPOSE: Although we have several established in vitro systems for studying the vasoactive properties of the ocular vasculature, the restricted availability of human donor tissue has forced us to rely predominantly on animal studies. METHODS: The present paper describes, for the first time, a controlled-rate cryopreservation technique capable of maintaining vasoactive function in human retinal arteries after extended storage. RESULTS/CONCLUSION: The response to constrictive (endothelin-I) and vasodilatory agents (nimodipine and betaxolol) was comparable with that in fresh pig vessels. It is now possible to obtain multiple segments of retinal artery from a single donor eye and to preserve them for detailed pharmacological assessment.

Aged↗

PubMed1998

Robotic ocular ultramicrosurgery.

BACKGROUND: There is an increasing need for improved microsurgical techniques in the eye. Delivery of small quantities of chemicals or cells into specific retinal locations, for example, cannot be achieved with hand-held instruments. The present paper describes the design principles used in the development of a robotic ocular ultramicrosurgical system and the results from preliminary animal trials. METHODS: We have developed a robotic ocular ultramicrosurgical system and a range of instruments for specific intraocular applications. RESULTS: We have successfully used the system for intravascular (< 70 microm) drug delivery, implantation of microdrainage devices and the intraretinal manipulation of microelectrodes with minimal damage. CONCLUSION: A clinically usable system using the same principles appears feasible.

Animals↗

PubMed1998

Quantification of retinal oxygen consumption changes from preretinal oxygen transients.

BACKGROUND: In the avascular retina of the guinea-pig all the oxygen supply is from the choroid. Under these circumstances we had proposed, on theoretical grounds, that a change in retinal oxygen consumption would modulate the preretinal oxygen level. METHODS: In the present study in guinea-pigs,the oxygen consumption of the outer retina was modulated by light-dark exposure while preretinal oxygen tension was monitored. RESULTS: The results were in complete agreement with the proposed mathematical models. CONCLUSION: The present study demonstrates that it is feasible to quantify oxygen consumption changes in a known retinal layer from measurements of preretinal oxygen tension.

Animals↗

PubMed1998

Culture and characterization of smooth muscle cells from porcine retinal microvessels.

PURPOSE: To establish long-term cultures of retinal vascular smooth muscle cells for future studies of their functions under normal and diseased conditions. METHODS: Smooth muscle cells (SMC) from porcine retinal microvessels were isolated and cultured. RESULTS: Cells in culture retained the common biochemical characteristics of SMC propagated from other sources. The cells were large, polygonal, spindle shaped and demonstrated the presence of smooth muscle-specific alpha-actin. Post-confluent cultures showed the 'hill and valley' multilayer growth characteristics. However, the growth rate was lower and the population doubling time was significantly larger than those reported for SMC propagated from big vessels. CONCLUSION: Retinal vascular SMC could be cultured separately from other cell types. The availability of this culture provides a unique model for functional and metabolic studies of the retinal vessels.

Actin Cytoskeleton↗

PubMed1998

Overview of studies on metabolic and vascular regulatory changes in early diabetic retinopathy.

The present review provides an overview of recent research describing functional changes to the retinal vasculature in very early diabetes. The research focuses on the streptozotocin rat model after 4-6 weeks of induced diabetes and describes functional changes to retinal blood flow, vascular control and retinal oxygenation, as well as a strong vasodilatory response to insulin in the retinal vasculature. The review raises the question of whether choroid dysfunction is also a feature of diabetic retinopathy.

Animals↗

PubMed1998

Relation between pressure determined by ophthalmodynamometry and aortic pressure in the dog.

AIMS: Ophthalmodynamometry has been used extensively since the last century; however, controversy surrounds what it actually measures. This study was set up to determine the relation between ophthalmodynamometric (ODP) and systemic blood pressures. METHODS: Aortic pressure was continuously monitored and altered by phlebotomy in six anaesthetised dogs, while ophthalmodynamometry was performed, by directly altering intraocular pressure. Maxillary artery pressure was monitored in two animals. All pressure transducers were zeroed at eye level. RESULTS: Mean ODP was 96.6% (1.6%) (95% confidence interval, n = 49) of aortic pressure. Mean maxillary artery pressure was 95.7% (5.5%) (95% CI, n = 16) of aortic pressure. ODP was 1.9 (0.6) mm Hg (95% CI, n = 33) higher than maxillary artery pressures. CONCLUSION: ODP was only slightly below aortic pressure and not significantly different from maxillary artery pressure, the analogue of the internal carotid artery in humans. These results also suggest a retinal artery collapse pressure of at least 1.9 mm Hg.

Animals↗

PubMed1998

Intraretinal oxygen distribution in urethan-induced retinopathy in rats.

This study was performed to explore the interaction between chronic neural degeneration and the subsequent vascular remodeling. Weekly urethan administration in rats from birth produces a retinopathy model characterized by photoreceptor degeneration, retinal vascular regression, and retinal pigment epithelium (RPE) neovascularization. We investigated the hypothesis that altered oxygen distribution across the retina and choroid could be involved in the vascular changes seen in this retinopathy. We compared measurements of vitreal, intraretinal, and choroidal oxygen tension (PO2) distribution in anesthetized and ventilated control and urethan-treated rats at 8 and 16 wk of age with the use of oxygen-sensitive microelectrodes. Striking differences were observed in both choroidal and intraretinal PO2 distribution in urethan-treated rats compared with controls. At both ages, intrachoroidal PO2 was much lower in the urethan-treated rats. In addition, the intraretinal PO2 distribution across the inner retinal layers was more uniform than normal. A small elevation in PO2 was present at 8 wk in the inner nuclear layer where subsequent vascular regression occurred, and a small reduction in PO2 was present at the RPE, which recovered to normal values by 16 wk in regions where RPE vessel networks were first evident. Although the retinal arteries were considerably thinner at both ages in the urethan-treated rats, the vitreal PO2 profiles and superficial retinal PO2 remained normal. The unexpected and large reduction in the oxygen delivery from the choroid found in the urethan-treated rats may account for the lack of major hyperoxia within the pathological retina and the lower oxygen tension in the RPE before the vascular proliferation in this region. We propose that tissue PO2 is an important determinant of the vascular remodeling, which is seen in this model of neural degeneration and that the PO2 distribution changes described in this study help provide a new view of the pathogenesis of this model.

Animals↗

PubMed1998

Pretreatment with glucocorticoid is essential for lactogenic induction of the bovine beta-casein/CAT expression in HC11 cells.

Hormonal regulation of the bovine beta-casein gene expression was studied in a murine mammary epithelial HC11 cells and compared with that of the rat beta-casein gene expression. CAT expression vectors driven by their promoter sequences were transfected into HC11 cells. Stable transfectents were treated with lactogenic hormones, dexamethasone and prolactin for 2 days in confluent cultures. While the lactogenic hormones synergistically induced a strong activation of the rat beta-casein/CAT expression, neither a single or combined treatment of dexamethasone and prolactin induced the bovine beta-casein/CAT expression. To test a sequential treatment effect of lactogenic hormones on the bovine beta-casein/CAT expression, cells were first treated with either dexamethasone or prolactin for various days and then subjected to the second treatment with both hormones for 2 days. Only dexamethasone-, but not prolactin-pretreated cells showed a strong lactogenic induction. Moreover, the fold induction of dexamethasone-pretreated cells increased gradually as a function of duration of dexamethasone pretreatment. A series of the bovine beta-casein/CAT constructs with different length of the bovine beta-casein 5' flanking region ranged from 0.3 kb to about 15 kb was analyzed in 12-days dexamethasone-pretreated cultures. CAT expression was increased even in 0.3 kb-containing construct, but prominent induction was seen in more than 1.8 kb-containing constructs. Therefore, it could be concluded that a long-term dexamethasone pretreatment is essential for lactogenic induction of the bovine beta-casein expression and the 0.3 kb proximal promoter region is important, but more distal promoter element(s) is necessary for mediating the coordinated action of lactogenic hormones to the bovine beta-casein expression.

Animals↗

PubMed1998

The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure.

PURPOSE: To measure the effects of cerebrospinal fluid pressure (CSFp) on retrolaminar tissue pressure (RLTp) and the translaminar pressure gradient (TLPG), particularly at low CSFp, which is the normal situation in erect posture. METHODS: Micropipettes coupled to a servonull pressure system were passed into eyes of anesthetized dogs to the optic disc and advanced in steps through the lamina cribrosa to the optic nerve subarachnoid space (ONSAS), while pressure measurements were taken. Cerebrospinal fluid pressure and intraocular pressure (IOP) were monitored and controlled. The TLPG was measured at varying IOPs and CSFps. The RLTp and ONSAS pressure (ONSASp) were measured at varying CSFps. In separate experiments, the optic nerve dura was incised, and pressure measurements were taken across the pia mater. RESULTS: The TLPG was strongly correlated to the difference between IOP and CSFp (r=0.93; n=18) when CSFp was more than zero. Mean RLTp was 3.7+/-0.2 mm Hg (SEM; n=15) when CSFp was 0 mm Hg. The ONSASp and RLTp were largely dependent on the presence of CSFp higher than break point pressures of -0.5 mm Hg and 1.33 mm Hg, respectively. However, below these break points, RLTp (slope 0.07) and ONSASp (slope 0.18) were little influenced by CSFp. Separate measurements across the pia mater revealed that 95% of the pressure drop occurred within 100 microm of the pial surface. CONCLUSIONS: The TLPG and RLTp are dependent on CSFp when CSFp is more than -0.5 mm Hg. Below this level, there is no hydrostatic continuity between the intracranial and optic nerve subarachnoid space. In this range, RLTp is stable and is little influenced by CSFp changes.

Animals↗

PubMed1997

Retinal artery and vein pressures in the dog and their relationship to aortic, intraocular, and cerebrospinal fluid pressures.

The relationship between retinal arterial (Pra) and aortic (Pa) pressures is unknown, and the relationship between retinal vein (Prv) pressure and intraocular pressure (IOP) is not clear. Also unclear is the effect of cerebrospinal fluid pressure (CSFp) upon retinal venous pressure. We aimed to measure the relationships among Pra, Prv, Pa, IOP, and CSFp. Dogs were anesthetized while IOP, CSFp, and Pa were monitored. Pipettes with 2.5-micron diameter tips, connected to a servonulling pressure transducer, were used to record pressures from the retinal arteries and veins. Across a range of IOP (16-22 mmHg), CSFp (0-21 mmHg), and Pa (23-195 mmHg) the Pra = 0.72 Pa + 4.3 (r = 0.99, n = 61, P < 0.01), which suggests that the relationship between Pra and Pa is linear over a broad range of systemic blood pressures. The correlation coefficient between Prv and IOP was greater than 0.96 (P < 0.01) at all venous sites and whether IOP was greater than or less than CSFp. The transmural pressure varied along the retinal vein from 1.3 +/- 0.3 mmHg (+/-95% CI, n = 30) at 1 disk diameter from the optic disk rim to 0.3 +/- 0.2 mmHg (n = 66) at the optic disk, with a 0.9-mmHg/mm pressure gradient. These are the first measurements demonstrating a retinal vein transmural pressure close to zero.

Animals↗

PubMed1997

Polymorphic sequence of Korean Native goat lactoferrin exhibiting greater antibacterial activity.

Lactoferrin, which exhibits antibacterial activity to protect infants from infectious disease, is a major component of colostrum and milk. Lactoferrin was purified from the colostrum of Korean Native goat, and the cDNA from the mammary gland mRNA of the animal was cloned and sequenced. The nucleotide sequence of the lactoferrin gene of Korean Native goat was found to differ in 15 sites from that of the goat lactoferrin gene reported earlier. This difference in nucleotide sequence resulted in six amino acid substitutions: five in the N-lobe and one in the C-lobe. The antibacterial activity of Korean Native goat lactoferrin was found to be greater than that of Sannen goat lactoferrin.

Amino Acid Substitution↗

PubMed1997

Measurement of vasoactivity in the guinea-pig choroid.

PURPOSE: A perfusion system for studying the vasoactive properties of the guinea-pig choroid is described. METHODS: The principle of operation is that the vascular resistance of the entire vascular network of an isolated, perfused eye can be monitored by recording the pressure required to deliver a constant flow of perfusate through the network. Delivery of the pharmacological agent of interest into the perfusate stream and the subsequent determination of the magnitude of any induced pressure changes allows the vasoactive potency of various agonists to be assessed. RESULTS: The baseline vascular resistance was 1.35 +/- 0.16 mmHg min/microL (mean +/- SEM; n = 10) and the mean response to intraluminal delivery of 124 mmol/L K+ Krebs was an increase in resistance of 297 +/- 67%. Vasoactive responses were sustainable for more than 8 h. CONCLUSIONS: This system will now be used to study the vasoactive properties of the guinea-pig choroid in greater detail.

Animals↗

PubMed1997

Hepatitis C virus envelope proteins bind lactoferrin.

Hepatitis C virus (HCV) has two envelope proteins, E1 and E2, which form a heterooligomer. During dissection of interacting regions of HCV E1 and E2, we found the presence of an interfering compound or compounds in skim milk. Here we report that human as well as bovine lactoferrin, a multifunctional immunomodulator, binds two HCV envelope proteins. As determined by far-Western blotting, the bacterially expressed E1 and E2 could bind lactoferrin in human milk directly separated or immunopurified and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The bindings of lactoferrin and HCV envelope proteins in vitro were confirmed by another method, the pull-down assay, with immunoprecipitated lactoferrin-bound protein A resin. By the same assay, mammal-expressed recombinant E1 and E2 were also demonstrated to bind human lactoferrin efficiently in vitro. Direct interaction between E2 and lactoferrin was proved in vivo, since anti-human lactoferrin antibody efficiently coimmunoprecipitated with secreted and intracellular forms of the E2 protein, but not glutathione S-transferase (GST), from lysates of HepG2 cells transiently cotransfected with the expression plasmids of human lactoferrin and gE2t-GST (the N-terminal two-thirds of E2 fused to GST) or GST. The N-terminal loop of lactoferrin, the region important for the antibacterial activity, has only a little role in the binding ability to HCV E2 but affected the secretion or stability of lactoferrin. Taken together, these results indicate the specific interaction between lactoferrin and HCV envelope proteins in vivo and in vitro.

Animals↗

PubMed1996

Asymmetrical response of the intraluminal and extraluminal surfaces of the porcine retinal artery to exogenous adenosine.

The relative effects of exogenous adenosine applied intraluminally or extraluminally were compared on first-order pig retinal arteries in an isolated perfused artery preparation. First-order retinal arteries with at least one side branch were cannulated and perfused at a constant flow in an environmentally-controlled organ bath on the stage of an inverted microscope. Vessels were precontracted with 10(-4) methoxamine applied extraluminally, which produced a sustained contraction. Then, either extraluminal or intraluminal adenosine was added in increasing concentrations from 10(-9) to 10(-3) M. During these procedures continuous measurements of external vessel diameter were made. The average external diameter of the retinal arterial segments used was 127.6 +/- 2.3 microns (n = 13). Extraluminal methoxamine (10(-4) M) constricted the vessels to 77.9 +/- 2.0% (n = 9) and 78.8 +/- 0.8% (n = 4) of the control value for the vessels later exposed to extraluminal and intraluminal adenosine respectively. Extraluminal adenosine caused a dose-dependent dilatation which commenced between 10(-7) M and 10(-6) M, and reached a percentage dilatation of 22.6 +/- 1.8% (n = 9) at 10(-3) M. For concentrations of 10(-4) M and above, spontaneous oscillations in diameter were observed for extraluminally-applied adenosine with an average period of 0.46 +/- 0.02 (n = 9) cycles per minute. The average percentage diameter oscillation was +/- 7.1% of the mean diameter. In contrast, intraluminal adenosine failed to cause dilatation or spontaneous oscillations at all concentration values, although the dilatory ability of these vessels was confirmed by intraluminal application of the Ca2+ channel blocker verapamil. In conclusion this study has demonstrated that the two sides of the retinal artery wall are differentially sensitive to adenosine, with the intraluminal route being ineffective. In vivo, in hypoxic or ischemic situations, adenosine is released by extraluminal neural tissue and minimizes tissue damage, partially by acting as a signaller of metabolic status to the vasculature leading to vasodilatation and hence increased local blood flow. This study shows that delivery of adenosine for therapeutic purposes through an intraluminal route is not a feasible proposition. This isolated, perfused artery technique has considerable potential to improve our understanding of uptake mechanisms, metabolism and vasoactivity of the retinal vessel wall.

Adenosine↗

PubMed1996

An efficient expression of human growth hormone (hGH) in the milk of transgenic mice using rat beta-casein/hGH fusion genes.

In order to produce human growth hormone (hGH) in the milk of transgenic mice, two expression vectors for hGH differing in their 3' flanking sequences were constructed by placing the genomic sequences of hGH gene under the control of the rat beta-casein gene promotor. The 3' flanking sequences of the expression constructs were derived from either the hGH gene (pBCN1GH) or the rat beta-casein gene (pBCN2GH). Transgenic lines bearing pBCN1GH expressed hGH more efficiently than those bearing pBCN2GH in the milk (19-5500 micrograms/mL vs 0.7-2 micrograms/mL). In particular, one of the BCN1GH lines expressed hGH as much as 5500 +/- 620 micrograms/mL. Northern blot analysis showed that the transgene expression was specifically confined to the mammary gland and developmentally regulated like the endogenous mouse beta-casein gene in the mammary gland. However, a low level of nonmammary expression was also detected with more sensitive assay methods. In conclusion, the rat beta-casein/hGH fusion gene could direct an efficient production of hGH in a highly tissue-and stage-specific manner in the transgenic mice and the 3' flanking sequences of hGH gene had an important role for the efficient expression.

Animals↗