Biomedical subjects

Ying Han

Publications and source records attributed to Ying Han.

At least 55 records · Page 3Linked to original sources

PubMed2005

[Studies on the anticancer effects of total alkaloid from Viscum coloratum].

OBJECTIVE: To study the anticancer effects of total alkaloid from Viscum coloratum in vivo and vitro. METHOD: In vitro, MTT assays were used t o measure the inhibitory effect. Cells at period of logarithmic growth were incubated for 24 hours. Then total alkaloid of various concentrations were added. 24 hours later, supernatant was removed and MTT was added. 4 hours after that, DMSO was added, then 30 minutes later, A value was measured. In vivo, suspension of carcinoma cells was implanted in the mice's limbs subcutaneously, 0.2mL each. 24 hours later, the mice were grouped randomly. Fed by total alkaloid continuously for 7 days, the mice were sacrificed. The tumors were weighed and calculated the inhibitory rates. RESULT: In vitro, it shows that total alkaloid has prominent inhibitory effect on the growth of carcinoma cells. In vivo, it shows that total alkaloid can inhibit the growth of tumors and prolong the survival days of the mice bearing tumors. CONCLUSION: Total alkaloid from Viscum coloratum has the activities of anticancer.

Alkaloids↗

PubMed2005

[Effect of endogenous heme oxygenase-carbon monoxide on brain damage induced by recurrent febrile seizures].

OBJECTIVE: Febrile seizures (FS) are the most common seizure disorders in children. Approximately one third of children with a febrile seizure have recurrent events. Although most FS may not represent a serious health problem, those that are more prolonged and recurrent may cause hippocampal damage which is the most important pathological basis of temporal lobe epilepsy. The present study aimed to explore the effect of endogenous heme oxygenase (HO)-carbon monoxide (CO) system on brain damage induced by recurrent FS. METHOD: Twenty-four Sprague-Dawley rats aged 21 days were randomly divided into three groups: Control group (immersed in 37.0 degrees C water, n = 8), FS group (immersed in 45.2 degrees C water, n = 8), FS + zinc protoporphyrin (ZnPPIX) group (immersed in 45.2 degrees C water, n = 8). FS in rats were induced ten times in a bath of warm water, once every 2 days. The indirect production of CO in plasma was detected by a dual wavelengh spectrophotometer. The intensity, latency, duration and rectal temperature of the seizure in rats were recorded. Morphologic changes of hippocampal neurons were observed with HE staining. The ultrastructural changes of the hippocampal neurons were observed under electron microscope. Semiquantitative analysis of hippocampal neurons was carried out by using Nissl stain. RESULT: After recurrent FS, the content of CO in plasma in FS group was increased as compared with that in control group (P < 0.01). The content of CO in plasma in FS + ZnPPIX group was decreased as compared with that in FS group (P < 0.01), while no significant difference in CO content was found as compared with that in control group (P > 0.05). In FS group, with the increase of seizure number, there was a trend of gradual prolongation of the seizure duration. In FS + ZnPPIX group, the seizure latency was gradually shortened and the seizure duration was further prolonged. There were no significant differences in seizure intensity and rectal temperature between the two groups. After recurrent FS, by using light microscope we could see that the arrangement of hippocampal neurons was disordered, polarity was not clear and vacuolization appeared in some neurons. At the same time the ultrastructure of hippocampal neurons under electron microscope changed, which manifested as mitochondrial swelling, dissolved and ruptured ridge and vacuole formation, and dilated rough endoplasmic reticulum (RER). ZnPPIX aggravated neuronal injury. No obvious loss of hippocampal neurons was observed in FS group, while the number of hippocampal neurons in CA(1) and CA(3) subfields in FS + ZnPPIX group decreased respectively as compared with that in FS group and in control group (P < 0.01 for all). CONCLUSION: The study by using ZnPPIX which is an inhibitor of HO showed that endogenous HO/CO might act as a protective factor in FS-induced brain damage.

Animals↗

PubMed2005

[Dipeptidyl peptidase IV gene expression in ovarian carcinoma cell lines with various maligant behaviour].

OBJECTIVE: To study the relationship between the expression of dipeptidyl peptidase IV (DPP IV) gene and malignant behavior of cells of ovarian carcinoma. METHODS: The differences of the malignant behavior of A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were examined by drawing cell proliferative curves, adhesive test, assay of incursion and chemotaxis. The expression of DPP IV among the cell lines and its relationship with the malignant behavior of ovarian carcinoma cell were detected by techniques of DPP IV activity assay, cytometry and reverse transcription polymerase chain reaction. RESULTS: Among all cell lines, the ability of proliferation, adhesion, incursion and chemotaxis of HO-8910PM were the highest, while those of A2780 were the lowest. The transcription of mRNA in A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were 0.7512 +/- 0.0012, 0.5596 +/- 0.0015, 0.3369 +/- 0.0009, and 0.2777 +/- 0.0006, respectively. The activity of DPP IV were 0.79 +/- 0.02, 0.64 +/- 0.03, 0.21 +/- 0.02, and 0.18 +/- 0.01, respectively; and the protein expression of DPP IV gene were 657.83 +/- 1.14, 538.53 +/- 5.29, 130.50 +/- 1.46, and 33.14 +/- 0.47, respectively, as assayed by cytometry. The correlation coefficients of the transcription of DPP IV gene and the adhesive, incursive and migratory ability of ovarian carcinoma cells were -0.987, -0.983, and -0.991, respectively; the correlation coefficients of the expression of DPP IV and those ability of cells were -0.959, -0.988, and -0.968; the correlation coefficients of the activity of DPP IV and those ability of cells were -0.952, -0.868, and -0.983. CONCLUSION: There is a negative correlation between the expression of DPP IV gene and the adhesive and incursive capability of cells of ovarian carcinoma.

Cell Adhesion↗

PubMed2005

[Lyophilization for platelet preservation].

To explore a new lyophilized preservation methods for human platelets, platelets were pre-treated with aldehyde, human albumin or trehalose was added to the system of condensed cooling as protectant to stabilize the structure of platelets. The optimal resuspending buffer was also selected in the study. The morphological changes of platelets were observed by using electron microscopy after lyophilization, and the expression of membrane proteins on platelets was detected also after lyophilization. The results indicated that the recovery rate of platelets treated with aldehyde was generally more than 60%. Aggregative ability was reduced a little than the platelet untreated. 5% of human albumin had an advantage over 40 mmol/L of trehalose in respect of the preservation effect. In the way of keeping aggregative ability, PPP was obviously better than PBS. The results of electron microscopy displayed that organelles including mitochondria and excreted granules could be observed distinctly. Whereas, expression of membrane proteins of platelet treated with aldehyde was evidently dropped as compared with those of the fresh platelet. In conclusion, aldehyde as a novel protective agent, has excellent effects on lyophilization of platelets and is worthy to be further studied.

Albumins↗

PubMed2005

[Tendency and mathematical model of relationship of blood ATP content with temperature and time of preservation].

To investigate the relationship of blood ATP content with temperature and time of preservation and to establish its mathematical model, adenosine triphosphate (ATP) concentration was applied as the index of the quality of erythrocytes; systematical study on variation of blood preserved in a series of different temperatures from 4 degrees C to 32 degrees C was performed, and a series of experimental data were obtained. The results showed that when the ATP concentration y = f (d, t, s) in preserved blood was given as the continuous function of the time (d), the temperature (t) and the initiate ATP concentration (s), the model was fitted with the theory of linearity regression in symbolic statistics, and the general mathematical physical equation of the variation of preserved blood quality was deduced. According to the equation, the whole blood in CPDA-1 solution could be efficiently stored for 35, 35, 29, 22, 18, 18, 13, 8, 7, 6, 6, 5, 4, 4 and 3 days in 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 degrees C, respectively. In conclusion, the general tendency of the variation of preserved blood quality according to the temperature and the time was systematically disclosed for the first time, which would be propitious to estimate the blood quality in various temperatures and to instruct clinical blood transfusion.

Adenosine Triphosphate↗

PubMed2004

Efficient synthesis of 4-aminoquinazoline and thieno[3,2-d]pyrimidin-4-ylamine derivatives by microwave irradiation.

[reaction: see text] A simple, efficient, and high-yielding synthesis of quinazolin-4-ylamine and thieno[3,2-d]pyrimidin-4-ylamine derivatives is reported under microwave irradiation conditions. Reaction conditions including temperature, solvent, and reaction time have been studied. An efficient parallel workup procedure was developed to generate a small library (23 compounds) in a short time period.

Journal Article↗

PubMed2004

Conformational flexibility of PEP mutase.

Previous work has indicated that PEP mutase catalyzes the rearrangement of phosphoenolpyruvate to phosphonopyruvate by a dissociative mechanism. The crystal structure of the mutase with Mg(II) and sulfopyruvate (a phosphonopyruvate analogue) bound showed that the substrate is anchored to the active site by the Mg(II), and shielded from solvent by a large loop (residues 115-133). Here, the crystal structures of wild-type and D58A mutases, in the apo state and in complex with Mg(II), are reported. In both unbound and Mg(II)-bound states, the active site is accessible to the solvent. The loop (residues 115-133), which in the enzyme-inhibitor complexes covers the active site cavity, is partially disordered or adopts a conformation that allows access to the cavity. In the apo state, the residues associated with Mg(II) binding are poised to accept the metal ion. When Mg(II) binds, the coordination is the same as that previously observed in the enzyme-Mg(II) sulfopyruvate complex, except that the coordination positions occupied by two ligand oxygen atoms are occupied by two water molecules. When the loop opens, three key active site residues are displaced from the active site, Lys120, Asn122, and Leu124. Lys120 mediates Mg(II) coordination. Asn122 and Leu124 surround the transferring phosphoryl group, and thus prevent substrate hydrolysis. Amino acid replacement of any one of these three loop residues results in a significant loss of catalytic activity. It is hypothesized that the loop serves to gate the mutase active site, interconverting between an open conformation that allows substrate binding and product release and a closed conformation that separates the reaction site from the solvent during catalysis.

Alanine↗

PubMed2004

[Detection of HPV16 E6 gene in cervical tissues by quantitative polymerase chain reaction].

OBJECTIVE: To establish a method for detection of Human Papillomavirus (HPV) type16 E6 gene in Cervical carcinomas Specimens. To study the relationship between the quantities of HPV16 E6 (Human papillomavirus type16 E6 gene) in cervical tissues and the course of cervical disease in Xinjiang. METHODS: HPV16E6 gene and beta-actin was detected in parallel by FQ-PCR (fluorescence quantitative PCR). The number of copies of HPV16 E6 gene and beta-actin was detected in parallel by FQ-PCR (fluorescence quantitative PCR) in tissues of 69 cervical cancer, 65 cervical intraepithelial neoplasia (CIN), 33chronic cervicitis and samples of 96 cervical smear samples of vaginitis and cervicitis. The variation in HPV copies per genomic DNA equivalent can be estimated by dividing the HPV copy number by the beta-actin copy number. RESULTS: The positive rate of HPV16 E6 gene was 83.0%, 75.7%, 93.3% and 3.3% in tissues of cervical cancer, cervical intraepithelial neoplasia (CIN), chronic cervicitis and samples of cervical smear respectively. The amount of HPV16 E6 gene was gradually higher by the developing of the course of cervical disease. They have positive rank correlation, r = 0.83, P < 0.01. CONCLUSION: The study underscores the importance of the relationship between the HPV16 E6 gene and the course of cervical disease in Xinjiang. It also suggests that the quantification of HPV16 E6 gene may be useful as a prognostic tool to identify women who are at increased risk of developing cervical cancer. This method may be applied to studies of a number of issues related to the natural history of cervical cancer, such as the amounts of HPV in high- and low-grade lesions.

Cervix Uteri↗

PubMed2004

Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy.

OBJECTIVE: To compare severity and locations of abnormalities detected by the multifocal electroretinogram (mfERG) and short-wavelength automated perimetry (SWAP) in diabetic eyes with early or no retinopathy. METHODS: One eye from each of 22 patients with diabetes mellitus who had early retinopathy and 18 patients with diabetes mellitus who had no retinopathy were tested on mfERG and SWAP. The mfERG implicit times were interpolated based on SWAP stimulus locations and compared with normative values obtained from 30 age-similar control subjects. The SWAP total threshold deviations were analyzed using an age-based control data set from 255 healthy subjects. The z scores of both measures were derived to allow measurement comparisons. RESULTS: Most responses for the 2 measurements were subnormal in both groups with diabetes mellitus. The 2 measurements showed a similar number of significant abnormalities (z score >/=2), about 40% and 20% of responses for diabetic patients with retinopathy and diabetic patients with no retinopathy, respectively. Local mfERG and SWAP results showed some spatial agreement for subjects with retinopathy (r = -0.38, P<.001) but not for those with no retinopathy. CONCLUSIONS: Both mfERG and SWAP are sensitive measurements of diabetic dysfunction, even prior to retinopathy. The lack of spatial correspondence between mfERG and SWAP abnormalities in diabetic patients with no retinopathy reflects overlapping, but different, retinal anomalies in early diabetic eye disease.

Adult↗

PubMed2004

Comparison of mfERG waveform components and implicit time measurement techniques for detecting functional change in early diabetic eye disease.

This study first compares two methods for measuring first order multifocal electroretinogram (mfERG) implicit time abnormalities in eyes with early diabetic retinopathy. Two analysis methods are used: template stretching (multiplicative scaling) of an 80 msec response epoch and template sliding (cross-correlation or additive scaling) of portions of responses containing the major waveform features. The study also compares the relative sensitivities of N1, P1 and N2 implicit time assessed by cross-correlation. The nature of the change in the mfERG waveform associated with diabetes is also assessed. MfERGs were recorded from 15 eyes of 15 individuals with diabetes and early non-proliferative retinopathy and 20 eyes of 20 healthy control subjects of similar age. Implicit time determined by template stretching is more frequently abnormal in the eyes of the diabetic subjects than the implicit time of any of the components assessed by template sliding. This is attributable to the lower variability of the template stretching implicit time measure in normals. Of the components, P1 is most often abnormal in the eyes of individuals with diabetes. Responses recorded from retinal areas with retinopathic signs are more often abnormal than those from other areas. Later components of the response are not delayed more than earlier ones. We conclude that template stretching is a sensitive measurement technique, but that it does not fully capture the effect of diabetes on the first order mfERG well.

Adult↗

PubMed2004

Oculomotor rehabilitation in acquired brain injury: a case series.

OBJECTIVE: To investigate the effects of systematic, oculomotor rehabilitation on basic versional ocular motility, as well as reading eye movements, in subjects with acquired brain injury, using objective eye movement recording and subjective rating of reading ability. DESIGN: Case series. SETTING: Clinical research laboratory. PARTICIPANTS: Two men with acquired brain injury: one with traumatic brain injury and one with stroke. INTERVENTIONS: Versional oculomotor training was performed for 1 hour, twice weekly for 8 weeks. There were 2 feedback modes of training: normal internal oculomotor visual feedback alone (4wk), or that feedback in conjunction with external oculomotor auditory feedback (4wk). Testing was conducted before and after training. Main outcome measures Objective outcome measures included both basic eye movement parameters (fixational accuracy, saccadic gain and latency, pursuit gain, mean saccade frequency ratio for simulated reading), and reading eye movement parameters (words per minute, grade level equivalent, fixations per 100 words, regressions per 100 words, percentage of reading comprehension, duration of fixation in seconds). Subjective outcome measures included the subject's ability to read based on the responses to the reading rating-scale questionnaire. RESULTS: Both subjects improved objectively in terms of basic versional oculomotor accuracy and reading ability. These findings concurred with their subjective impressions. CONCLUSIONS: This case series provides objective documentation of the positive effects of oculomotor rehabilitation on basic ocular motility and reading ability in selected cases with acquired brain injury, thus suggesting the need for a larger clinical trial in this area.

Adult↗

PubMed2004

Reading-related oculomotor testing and training protocols for acquired brain injury in humans.

Many individuals with acquired brain injury (ABI) report reading problems of oculomotor origin. These may include frequent loss of place, skipping of lines and difficulty shifting to the next line of print. We describe two protocols for the testing and training of reading-related eye movements in adult individuals with ABI (traumatic brain injury [TBI] and stroke with hemianopia), who experience oculomotor-based symptoms when reading. These protocols use objective eye movement recording techniques and computer-based stimulus presentation and analysis. One protocol tests and the other trains basic horizontal and vertical versional eye movements (fixation, saccades and pursuit), as well as reading eye movements using simulated single and multiple line dynamic arrays. In addition, a reading rating-scale questionnaire is administered before and after completion of training to assess subjective reading improvement. In all paradigms, the target consists of a 0.5 degrees luminous square, which is displayed on a computer monitor positioned 40 cm from the subject along the midline. All testing and training are conducted under binocular viewing conditions with optical correction in place. There are two modes of training: normal internal oculomotor visual feedback either alone (4 weeks) or in conjunction with external oculomotor auditory feedback (4 weeks) administered in a counterbalanced manner within each diagnostic group. Training is performed 1 h, twice weekly for the 8 weeks. Oculomotor testing is conducted before, midway and after training. Following training, reading-related eye movements and reading ability improved as assessed both subjectively and objectively. These protocols provide a systematic approach to the quantitative and comprehensive testing and training of reading-related eye movement skills and behaviors in the ABI population manifesting oculomotor-based reading dysfunctions. Furthermore, the training protocol results in the rapid remediation of the eye movement deficits, which appear to transfer to activities of daily living.

Brain Injuries↗

PubMed2004

Twinned principal curves.

Principal Curves are extensions of Principal Component Analysis and are smooth curves, which pass through the middle of a data set. We extend the method so that, on pairs of data sets which have underlying non-linear correlations, we have pairs of curves which go through the 'centre' of data sets in such a way that the non-linear correlations between the data sets are captured. The core of the method is to iteratively average the current local projections of the data points which produces an increasingly sparsified set of nodes. The Twinned Principal Curves are generated in three ways: by joining up the nodes in order, by performing Local Canonical Correlation Analysis and by performing Local Exploratory Correlation Analysis (Koetsier et al., 2002). The latter two are shown to improve the forecasting capability of the method but at an increased computational load. We show that it is crucial to terminate the algorithm after a small number of iterations for the first method and investigate several criteria for doing so.

Algorithms↗

PubMed2004

Retinal function in normal and diabetic eyes mapped with the slow flash multifocal electroretinogram.

PURPOSE: It has been suggested that late components of the standard multifocal electroretinogram (mfERG) are preferentially affected by diabetes mellitus. The slow-flash (sf-)mfERG stimulates with flashes separated by dark periods, facilitating interpretation of late first-order response components compared with standard multifocal stimulation. Retinal function and response component changes were examined using the sf-mfERG in diabetic subjects with and without diabetic retinopathy. METHODS: Eighteen control subjects, 12 diabetic patients without retinopathy and 17 diabetic patients with nonproliferative diabetic retinopathy (NPDR), were tested monocularly. A total of 103 areas of the central 45 degrees were stimulated by pseudorandom 100-cd/m2 flashes separated by at least 53.3 ms. Major components and the amplitude of the first-order sf-mfERGs were examined. Each subject's N1, P1, and N2 implicit times (ITs) and scalar product amplitudes (SPs) were measured at all 103 retinal locations and converted into z-scores based on the control values. Abnormalities were defined as z-scores greater than 2.33 (P < 0.01). RESULTS: Local functional abnormalities were found in both the diabetic patients with NPDR and in those without retinal disease. In both groups of diabetic patients, most abnormalities occurred more frequently in the inferior retina. Later components (P1 and N2) of the local sf-mfERGs were not preferentially affected by diabetes. The local SP and P1 IT measures distinguished the subject groups better than N1 IT and N2 IT. CONCLUSIONS: Local functional retinal abnormalities in diabetic persons with or without NPDR can be detected and mapped by the sf-mfERG. Diabetes and NPDR do not, however, preferentially affect the late P1 and N2 response components.

Diabetes Mellitus, Type 1↗

PubMed2004

Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy.

PURPOSE: To examine the potential of abnormal mfERGs to predict the development of diabetic retinopathy at corresponding retinal locations 1 year later. METHODS: One eye of 11 diabetic patients with nonproliferative diabetic retinopathy (NPDR) and 11 diabetic patients without retinopathy were retested 12 months after initial testing. At each time, mfERGs were recorded from 103 retinal locations, and fundus photographs were taken within 1 month of each recording. Local mfERG implicit times were measured and their z-scores were calculated based on results obtained from 20 age-matched control subjects. mfERG abnormalities were defined as z-scores of 2 or more for implicit time and z-scores of -2 or less for amplitude (P < or = 0.023). mfERG z-scores were mapped onto fundus photographs, and the relationship between baseline abnormal z-scores and new retinopathy at follow-up was examined. RESULTS: New retinopathy developed in 7 of the eyes with NPDR after 1 year. In these eyes, 70% of the mfERGs in areas of new retinopathy had abnormal implicit times at baseline. In contrast, only 24% of the responses in regions that remained retinopathy free were abnormal at baseline. Relative risk of development of new retinopathy over 1 year in the areas with abnormal baseline mfERG implicit times was approximately 21 times greater than that in the areas with normal baseline mfERGs (odds ratio = 31.4; P < 0.001). Eyes without initial retinopathy did not develop new retinopathy within the study period, although 4 of these 11 eyes had abnormal implicit times at baseline. mfERG implicit times tended to be more delayed at follow-up than at baseline in NPDR eyes, but not in eyes without retinopathy and control eyes. mfERG amplitudes had no predictive power. CONCLUSIONS: Localized functional abnormalities of the retina reflected by mfERG delays often precede the onset of new structural signs of diabetic retinopathy. Those functional abnormalities predict the local sites of new retinopathy observed 1 year later.

Adult↗

PubMed2004

Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy.

PURPOSE: To study retinal dysfunction in diabetes and early nonproliferative diabetic retinopathy (NPDR) using a new method to analyze local multifocal electroretinogram oscillatory potentials (mfOPs). METHODS: One eye of each of 26 normal subjects, 16 diabetic subjects without retinopathy (NoR), and 16 diabetic subjects with early NPDR was examined. Slow-flash multifocal electroretinograms (sf-mfERGs) were recorded from the central 45 degrees, and stereo fundus photographs of the diabetic eyes were taken. The first-order (K1), induced first-order (K1i), and second-order (K2) response components were extracted from each retinal location, and K1i and K2 were added to create Ks2. Responses from 35 contiguous areas were digitally filtered 90 to 225 Hz to isolate the mfOPs. The signal-to-noise ratio (SNR) of the mfOPs was calculated, and abnormality was defined as SNR below the fifth percentile of the normal subjects. RESULTS: Combining the K1i and K2 components to form Ks2 before isolation of the mfOPs by digital filtering increased the SNR. Mean Ks2 and K1 mfOP SNRs were abnormal in 25% and 19% of the NoR eyes, respectively, and both were abnormal in 62% of the NPDR eyes. The retinal distributions of the local Ks2 and K1 mfOP abnormalities overlapped, but they differed. Furthermore, local Ks2 mfOP abnormalities were preferentially associated with retinal sites containing NPDR but K1 mfOP abnormalities were not. CONCLUSIONS: The cells that contribute to the generation of local mfOPs are affected by diabetes and, to a greater degree, by early NPDR. The results suggest that fast adaptive mechanisms influencing the mfOPs are most abnormal at retinal sites containing NPDR.

Adult↗

PubMed2004

Formulation and evaluation of a predictive model to identify the sites of future diabetic retinopathy.

PURPOSE: To formulate and test a model to predict the development of local patches of nonproliferative diabetic retinopathy (NPDR), based on multifocal electroretinogram (mfERG) implicit times and candidate diabetic risk factors. METHODS: mfERGs and fundus photographs were obtained from 28 eyes of 28 diabetic patients during an initial and 12-month follow-up examination. mfERG implicit times were derived at 103 locations using a template-stretching method, and a z-score was calculated in comparison with 20 age-matched normal subjects. Thirty-five nonoverlapping retinal zones were constructed by grouping two to three adjacent stimulated locations, and each zone was assigned the maximum z-score within it. Zones containing initial retinopathy were excluded from further analysis. The probability that new retinopathy would develop in the remaining zones by the follow-up examination was modeled based on the mfERG implicit time z-score for the zone and other candidate diabetic risk factors determined during the initial visit. Data collected from four previously untested diabetic subjects and the other eye of eight previous subjects during their second year follow-up were used to test the predictive model. RESULTS: After 1 year, new retinopathy developed in 11 of the 12 NPDR eyes and 1 of the 16 eyes without initial retinopathy. After accounting for the correlation among zones within each eye, a predictive model was formulated with the variables mfERG implicit time, duration of diabetes, presence of retinopathy (NPDR or no retinopathy), and blood glucose level at initial visit. The area under the receiver operating characteristic (ROC) curve of this multivariate model is 0.90 (P <0.001). The predictive model has an expected sensitivity of 86% and a specificity of 84%, which was verified by the test data. CONCLUSIONS: The development of diabetic retinopathy over a 1-year period can be well predicted by a multivariate model. The inclusion of local mfERG implicit times allowed the model to identify the specific sites of future retinopathy.

Adult↗

PubMed2004

FAS-mediated apoptosis and its relation to intrinsic pathway activation in an experimental model of retinal detachment.

PURPOSE: To determine whether the FAS-mediated apoptosis pathway becomes activated in the retina after retinal detachment and to investigate the temporal relationship between the activation of the FAS-pathway and the intrinsic apoptosis pathway involving caspase-9 and cytochrome c. METHODS: Experimental retinal detachments were created in Brown-Norway rats by injecting 10% hyaluronic acid into the subretinal space. Retinal tissue was harvested at 2, 4, 8, 24, 72, and 168 hours after creation of the detachment. Immunoprecipitation was performed to assess for FAS-receptor/FAS-ligand complex formation, and activation of caspase-8 and BID (a member of the Bcl-2 family of proteins) was assessed by Western blot analysis. A caspase-9 activity assay and immunoprecipitation of the caspase-9/cytochrome c complex were performed at these same time points. Specific pathway inhibition was performed with the caspase-9 inhibitor zLEHD.fmk or neutralizing antibodies against either the FAS-receptor or FAS-ligand. Transcription levels of FAS and intrinsic pathway intermediates were assessed as a function of time after retinal detachment by using quantitative real-time polymerase chain reaction. RESULTS: Retinal detachment resulted in the time-dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak of caspase-9 activity and caspase-9/cytochrome c complex formation. Cleavage of caspase-8 and truncation of BID were also observed. Injection of zLEHD.fmk into the subretinal space of a detached retina resulted in decreased caspase-9 activity, as did injection of anti-FAS-receptor antibody into either the subretinal space or the vitreous. Retinal detachment resulted in the transcriptional upregulation of the FAS-receptor, FAS-ligand, caspase-8 and BID, but not caspase-9 and cytochrome c. CONCLUSIONS: The FAS-mediated apoptosis pathway becomes activated and transcriptionally upregulated after retinal detachment. The peak of FAS activation precedes that of the intrinsic pathway, and inhibition of FAS activation can decrease caspase-9 activity.

Animals↗