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Biomedical subjects

Y Kitazawa

Publications and source records attributed to Y Kitazawa.

At least 19 recordsLinked to original sources

Serum autoantibodies to heat shock proteins in glaucoma patients from Japan and the United States.

OBJECTIVE: To study serum titers of antibodies against heat shock proteins in glaucoma patients from two different ethnic populations and to examine the relationship between serum antibody titers and glaucomatous damage. STUDY DESIGN: Comparative, cross-sectional study. PARTICIPANTS: Twenty-seven age-matched patients with primary open-angle glaucoma, 28 patients with normal pressure glaucoma, and a control group of 26 healthy subjects from Japan; and 21 age-matched patients with primary open-angle glaucoma, 40 patients with normal pressure glaucoma, and a control group of 20 healthy subjects from the United States. MAIN OUTCOME MEASURES: Measurement of serum antibody titers and examination of optic disc and visual field parameters. METHODS: Serum immunoreactivity against heat shock proteins, including hsp27, alphaB-crystallin, and human and bacterial hsp60, was studied by enzyme-linked immunosorbent assay (ELISA). The relationship of serum antibody titers to glaucoma parameters, including mean deviation, neural rim area-to-disc area ratio, and peripapillary atrophy area-to-disc area ratio was examined. RESULTS: The serum ELISA titers of antibodies, including hsp27, alphaB-crystallin, human hsp60, and bacterial hsp60 antibodies, were higher in glaucoma patients compared with control subjects in both the Japanese and American groups (P: < 0.05). There was no association between the serum antibody titers and optic disc parameters in either group from Japan or the United States (P: > 0.05). CONCLUSIONS: These findings suggest that increased titers of circulating antibodies against heat shock proteins occur in both Japanese and American patients with glaucoma. The lack of a relationship between the level of serum antibody titers and the degree of glaucomatous damage in either ethnic group suggests that increased antibodies to heat shock proteins do not occur as an epiphenomenon of the glaucomatous neurodegeneration process.

Aged↗

[Blood flow in retinal vessels of normal-tension glaucoma with or without a history of optic disc hemorrhages].

PURPOSE: To evaluate blood flow in retinal vessels of normal-tension glaucoma (NTG) with or without a history of optic disc hemorrhages (DH) and compare it with that in non-glaucomatous eyes using scanning laser fluorescein video angiography. METHODS: We enrolled 14 eyes of 14 NTG patients with a history of DH (DH (+) group), 12 eyes of 12 NTG patients without history of DH (DH (-) group), and 10 eyes from 10 non-glaucomatous patients matched for age, intraocular pressure, and systemic blood pressure. No statistically significant difference was observed between the DH (+) and DH (-) groups of NTG in the global indices of the Humphrey visual field. Fluorescein angiography was performed using a scanning laser ophthalmoscope with an argon blue laser. A series of approximately 100 consecutive video images at 1/2 second intervals from just before the dye appearance in the central retinal artery was loaded into an external personal computer system. Based on this acquired image series, we obtained fluorescein filling curves for 10 x 10 pixel measuring areas placed on each of the superior-temporal and inferior-temporal branch retinal arteries and veins at 1/5 papillary diameter from the disc edge. In each vessel, time to the highest fluorescein intensity (peak time, sec) and the time constant of the filling curve (tau, sec) were obtained. Time difference between the peak times in vein and artery (peak time difference) was also calculated. RESULTS: Statistically significant differences were observed among the three groups in the peak time of inferior-temporal artery and vein, and superior-temporal vein (ANOVA, p < 0.01). Also there were statistically significant differences in the tau of all vessels (ANOVA, p < 0.05). No statistically significant differences were observed in the peak time differences. By multivariate analysis, the DH (+) and DH (-) groups of NTG showed significantly longer peak times and tau s than did the non-glaucomatous eyes (p < 0.05). However, no statistically significant differences were observed in any parameters between the DH (+) and DH (-) groups of NTG. CONCLUSIONS: In NTG, dye filling rate in both the central retinal arteries and veins seems to be delayed. However, this delay does not differ between DH (+) and DH (-) groups.

Aged↗

Optic Disc Blood Flow Measured by Scanning Laser-Doppler Flowmetry Using a New Analysis Program.

Purpose: Using a new analysis program for scanning laser-Doppler flowmetry (SLDF) by a Heidelberg retina flowmeter (HRF), we studied the relation between flow and visual field or disc morphology.Subjects and Methods: In 42 eyes of 21 patients with normal tension glaucoma (NTG) the mean-flow of the HRF blood flow parameters at the disc rim was measured and analyzed by a new analysis program for perfusion maps (the SLDF analysis tool), to minimize the influence of large vessels or/and artifacts caused by small eye movements. We investigated whether difference of the mean-flow between a pair of eyes had any relation to differences between a pair of eyes in visual field indices and those in disc morphological measurements of the Heidelberg retina tomograph.Results: We found statistically significant correlations between the mean-flow and optic disc parameters (Disk Area, Cup Area, Height Variation Contour, Cup Volume, Rim Volume, Mean RNFL Thickness). We found no statistically significant correlations between the mean-flow and visual field parameters (mean deviation, corrected pattern standard deviation).Conclusion: The results suggested that eyes with less flow in the optic disc rim have more advanced glaucomatous morphological changes.

Journal Article↗

The effect of mitomycin C trabeculectomy on the progression of visual field defect in normal-tension glaucoma.

BACKGROUND: We investigated in a prospective fashion the visual prognosis and complications in normal-tension glaucoma following unilateral trabeculectomy with adjunctive mitomycin C. METHODS: Trabeculectomy with adjunctive mitomycin C was carried out unilaterally in 21 cases of normal-tension glaucoma. Intraocular pressure (IOP), visual prognosis, and complications were compared between the operated eyes and the non-operated fellow eyes. The follow-up period ranged from 2 to 7 years. RESULTS: The IOP dropped significantly from 14.8+/-1.8 mmHg (mean +/- SD) to 9.6+/-3.9 mmHg in the operated eyes (P=0.0002, Wilcoxon signed-rank test), but did not drop in the non-operated eyes. The mean deviation (MD) was -12.69+/-6.41 dB preoperatively and -14.70+/-5.49 dB at the last clinic visit in the operated eyes, whereas in non-operated eyes it was -7.85+/-5.65 dB and -11.15+/-5.62 dB, respectively. The MD deteriorated significantly in both operated and non-operated eyes (operated eyes P=0.0239, non-operated eyes: P=0.0002; Wilcoxon signed-rank test). The MD slope was -0.37+/-0.60 dB/year and -0.71+/-0.89 dB/year for the operated and non-operated eyes, respectively (P=0.5243, Mann-Whitney U-test). Visual field deterioration was more frequently observed in the non-operated eyes by a pointwise definition of the progression (P<0.05, McNemar test). Visual acuity deteriorated in 6 of the operated eyes and in 5 of the non-operated eyes. Cataract developed in 6 (29%) of the 21 operated eyes, while among the non-operated eyes 4 (19%) developed cataract. CONCLUSION: Mitomycin C trabeculectomy is effective in delaying progression of visual field defect in normal-tension glaucoma, but complications may arise and cause some visual disturbance.

Adult↗

Disk hemorrhage is a significantly negative prognostic factor in normal-tension glaucoma.

PURPOSE: We investigated the relationship between disk hemorrhage in normal-tension glaucoma and the progression of visual field defects and, additionally, whether hemorrhage plays a role in the pathogenic process of the chronic disease. METHODS: We retrospectively reviewed the charts of 70 patients with normal-tension glaucoma (mean follow-up, 5.6 years) who were not medicated for glaucoma, and we applied a regression analysis of survival data based on the Cox proportional hazards model. Several clinical factors were investigated to find a possible association with the progression of glaucomatous visual field defined by two different definitions: one by mean deviation change and the other by glaucoma change probability analysis. RESULTS: Disk hemorrhage, corrected-pattern standard deviation, age, systolic blood pressure, and pulse rate had a significant influence on the visual field defect. The cumulative probability of progression of visual field loss was significantly greater for patients with disk hemorrhage than for patients without disk hemorrhage by either criterion for progression (P </=.0008, logrank test). All eyes that had at least two occurrences of disk hemorrhage showed progression, whereas only three of nine eyes showed progression in the nonrecurrent disk hemorrhage group by the glaucoma change probability analysis. The difference was statistically significant (P <.0001, Fisher's exact probability test). Furthermore, there was a significant relationship between the location of the disk hemorrhage and the area of the progression of visual field loss in 65.4% of progressive patients with disk hemorrhage. CONCLUSIONS: Several clinical factors other than intraocular pressure are significantly associated with the progression of visual field loss during the natural course of normal-tension glaucoma. Among these, disk hemorrhage is a significantly negative prognostic factor in patients with normal-tension glaucoma and may be a sign of progressive damage of the retinal nerve fiber layer, leading to functional deterioration of the visual field.

Adult↗

Retrobulbar hemodynamics in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure.

PURPOSE: To investigate retrobulbar hemodynamics by means of color Doppler imaging in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure. METHODS: Forty-nine consecutive patients who met the enrollment criteria were enrolled in a prospective study. We measured intraocular pressure at 2-hour intervals for 24 hours and performed color Doppler imaging of the orbital arteries, 48-hour ambulatory blood pressure monitoring, and visual field testing. Color Doppler parameters were compared between subjects with higher ocular perfusion pressure in the eye that had a better mean deviation (concordant group) and worse mean deviation (discordant group). RESULTS: In the eyes with the better mean deviation, the end-diastolic velocity of the ophthalmic artery was significantly slower in the discordant group (P=.0145), while in the eyes with the worse mean deviation, the peak systolic and end-diastolic velocities of the ophthalmic artery were significantly slower and the resistance index of the ophthalmic artery was significantly higher in the discordant group (P=.0395, P=.0088, and P=.0324, respectively). In the concordant group, the end-diastolic velocity of the central retinal artery was slower in eyes with a worse mean deviation. CONCLUSION: Retrobulbar hemodynamics are significantly altered in patients with normal-tension glaucoma who have better ocular perfusion pressure in the eye that has a worse mean deviation.

Adult↗

Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glaucoma.

PURPOSE: To investigate the relationship between the effect of carbon dioxide (CO2) inhalation or oral nilvadipine, a calcium-channel blocker, on orbital blood flow in patients with normal-tension glaucoma, as determined by color Doppler imaging. PATIENTS AND METHODS: Sixteen patients with normal-tension glaucoma (mean age, 55.6+/-9.8 years; male:female ratio, 3:13) underwent color Doppler imaging to measure the resistance index, and peak systolic and end-diastolic blood flow velocities of the ophthalmic artery, central retinal artery, and nasal and temporal short posterior ciliary arteries. Measurements were taken before and during CO2 supplementation sufficient to increase the end-tidal CO2 partial pressure by 10%. The color Doppler imaging measurements were repeated after 2 to 4 weeks of treatment with 2 mg oral nilvadipine, and comparisons were made between the effects of the two treatments. RESULTS: Both CO2 inhalation and nilvadipine treatment significantly reduced the resistance index in the central retinal artery, nasal short posterior ciliary artery, and temporal short posterior ciliary artery. There was a significant correlation between the effects of the two treatments on the difference in the resistance indexes of the ophthalmic artery and central retinal artery, but not on those of the nasal or temporal short posterior ciliary artery. CONCLUSIONS: Both CO2 inhalation and oral nilvadipine significantly reduce the resistance index measured by color Doppler imaging in orbital vessels. The effect of oral nilvadipine might be predicted by CO2 inhalation in patients with normal-tension glaucoma.

Administration, Inhalation↗

Changes in the nerve fiber layer thickness following a reduction of intraocular pressure after trabeculectomy.

PURPOSE: To assess changes in the nerve fiber layer thickness after trabeculectomy using scanning laser polarimetry. METHODS: The authors prospectively enrolled 46 eyes from 46 patients with primary open-angle glaucoma in whom intraocular pressure had been reduced by more than 30% after trabeculectomy without significant ophthalmic complications and from whom good quality images were obtained by a scanning laser polarimetry preoperatively and at 3 to 6 months after trabeculectomy. In each enrolled eye, changes in the nerve fiber layer thickness after surgery in the defined ring (1.8 disc diameters) around the optic disc were calculated in 10 degrees intervals (36 sectors in total) and in the following 4 quadrants (the sum of 9 10 degrees sectors): superior, nasal, inferior, and temporal. RESULTS: The mean intraocular pressure was 22.6 +/- 6.9 mm Hg preoperatively and 10.2 +/- 3.7 mm Hg postoperatively (P < 0.01). According to the analyses in every 10 degrees, the postoperative nerve fiber layer thickness was significantly greater than the preoperative nerve fiber layer thickness in the superotemporal region (10-50 degrees) and inferotemporal region (290-340 degrees) of the optic disc (P < 0.05). A stepwise multiple regression analysis showed that only the preoperative mean deviation in the Humphrey visual fields was a significant independent factor associated with changes in the nerve fiber layer thickness in the nasal and inferior quadrants. CONCLUSIONS: The thickness of the nerve fiber layer, as measured by scanning laser polarimetry, may increase after trabeculectomy, especially in the superotemporal and inferotemporal regions, and can be expected in cases in the early stage of glaucoma that have a better mean deviation.

Diagnostic Techniques, Ophthalmological↗

Scaling behaviors of branched polymers

We study the thermodynamic behavior of branched polymers. We first study random walks in order to clarify the thermodynamic relation between the canonical ensemble and the grand canonical ensemble. We then show that correlation functions for branched polymers are given by those for straight phi(3) theory with a single mass insertion, not those for the straight phi(3) theory themselves. In particular, the two-point function behaves as 1/p(4), not as 1/p(2), in the scaling region. This behavior is consistent with the fact that the Hausdorff dimension of the branched polymer is 4. In the appendixes we derive the exact two-point correlation function at finite (but large) system size N, which is consistent with the analysis in the body of the paper.

Journal Article↗

[Neuroprotective effect of N-methyl-D-aspartate receptor antagonists in an experimental glaucoma model in the rat].

PURPOSE: To evaluate the neuroprotective effect of memantine and dizocilpine, which are noncompetitive open-channel blockers of the N-methyl-D-aspartate (NMDA) receptor, on glaucomatous optic neuropathy in an experimental glaucoma model in the rat. METHODS: Experimental glaucoma was induced in the right eyes of 30 Wistar albino rats by intracameral injection of India ink followed by laser trabecular photocoagulation 4 days later. The left eye served as a control. Either memantine, dizocilpine, or phosphate-buffered saline (PBS) was injected intraperitoneally just before trabecular photocoagulation. Five days later, 3% fast blue was injected into both superior colliculi. The eyes were enucleated another 3 days later and flat mounts of the retinas were prepared. Labeled ganglion cells were counted in the area 1 mm away from the optic disc. RESULTS: Five days after laser application, no significant intraocular pressure (IOP) change in the right eye was found among the 3 groups. In eyes treated with memantine or dizocilpine, significantly more ganglion cells were labeled. CONCLUSION: Systemically applied memantine and dizocilpine had a neuroprotective effect against experimental glaucomatous optic neuropathy in the rat.

Animals↗

[Mitomycin C dissolved in a reversible thermo-setting gel: effect on aqueous flare in the rabbit eye].

PURPOSE: To determine the effects of mitomycin C (MMC) dissolved in a gel, which is as effective as a higher dose of aqueous MMC solution, on aqueous flare in rabbits. METHOD: We injected subconjunctivally a 0.1 ml solution of MMC containing 30, 10, 3.0, or 0.3 micrograms of MMC dissolved in a reversible thermo-setting gel in pigmented rabbits. As a control, a 0.1 ml aqueous solution of 30 micrograms MMC was injected subconjunctivally. Aqueous flare was measured for 28 days after the injection. RESULTS: The aqueous flare in the 30 micrograms gel group was also level similar to that in the 30 micrograms aqueous solution group, but the aqueous flare in the 10, 3.0, and 0.3 micrograms gel groups was significantly lower. The increase in the aqueous flare following the administration of MMC gel was dose-dependent. CONCLUSION: The administration of MMC dissolved in a gel can diminish the ocular inflammation by reducing the dose of MMC needed for the antiproliferative effect.

Animals↗

[Optic disc blood flow measured by scanning laser-Doppler flowmetry using a new analysis program].

PURPOSE: Using a new analysis program for scanning laser-Doppler flowmetry (SLDF) by a Heidelberg retina flowmeter (HRF), we studied the relation between flow and visual field or disc morphology. SUBJECTS AND METHODS: In 42 eyes of 21 patients with normal tension glaucoma (NTG) the mean-flow of the HRF blood flow parameters at the disc rim was measured and analyzed by a new analysis program for perfusion maps (the SLDF analysis tool), to minimize the influence of large vessels or/and artifacts caused by small eye movements. We investigated whether difference of the mean-flow between a pair of eyes had any relation to differences between a pair of eyes in visual field indices and those in disc morphological measurements of the Heidelberg retina tomograph. RESULTS: We found statistically significant correlations between the mean-flow and optic disc parameters (Disk Area, Cup Area, Height Variation Contour, Cup Volume, Rim Volume, Mean RNFL Thickness). We found no statistically significant correlations between the mean-flow and visual field parameters (mean deviation, corrected pattern standard deviation). CONCLUSION: The results suggested that eyes with less flow in the optic disc rim have more advanced glaucomatous morphological changes.

Adult↗

Regulation of connexin phosphorylation and cell-cell coupling in trabecular meshwork cells.

PURPOSE: To investigate the expression of functional gap junctions and the effect of protein kinase C (PKC) on such junctions in confluent cultures of bovine trabecular meshwork (TM) cells. METHODS: Expression of the gap junction protein connexin43 in TM cells was examined by immunofluorescence microscopy. Intercellular communication by gap junctions was assessed by observing the diffusion of fluorescent dye from an individual cell injected with lucifer yellow. The phosphorylation of connexin43 was evaluated by immunoblot analysis with a monoclonal antibody to this protein. RESULTS: Immunofluorescence staining revealed that connexin43 was localized to sites of contact between adjacent TM cells. Exposure of cells to the PKC activator phorbol 12-myristate 13-acetate (PMA; 10 nM, 1 hour) had no marked effect on the pattern of connexin43 immunofluorescence. Injection of a TM cell with lucifer yellow resulted in the spread of the dye into neighboring cells. Dye coupling was inhibited by PMA in a dose- and time-dependent manner, and this inhibition was prevented by pretreatment of cells with the PKC inhibitor bisindolylmaleimide I. Immunoblot analysis of control TM cell lysates yielded connexin43 bands corresponding to the nonphosphorylated protein (43 kDa) and three phosphorylated forms (47, 48, and 49 kDa). Cells exposed to PMA (10 nM, 1 hour) yielded an additional band corresponding to a 44-kDa form of phosphorylated connexin43 and showed a decrease in the intensity of the band corresponding to the nonphosphorylated protein and an increase in the intensity of the 47-kDa band. CONCLUSIONS: TM cells communicate with each other through gap junctions, and the communication is inhibited by PKC, probably, at least in part, through phosphorylation of connexin43.

Actins↗

Transient ischemic injury in the rat retina caused by thrombotic occlusion-thrombolytic reperfusion.

PURPOSE: To establish a clinically relevant model of transient retinal ischemia by thrombotic occlusion-thrombolytic reperfusion of the central retinal artery of the rat. METHODS: Thrombus was photochemically induced in the central retinal artery by the combination of intravenous injection of photo-sensitive dye, rose bengal, and green laser irradiation focused on the artery. Transient retinal ischemia for 60 minutes was achieved by a subsequent systemic administration of tissue-type plasminogen activator to reperfuse the occluded vessel. Samples of retinas were excised from the animals killed 3, 9, 12, 24, 48, and 78 hours after the reperfusion. The experimental data were processed using the TdT-dUTP terminal nick-end labeling (TUNEL) method to detect apoptotic cells. RESULTS: The transient retinal ischemia caused time-sequential apoptotic changes in the retinal cells as evaluated by counting the number of TUNEL-positive cells. The most remarkable changes occurred in the central area of retina, and further on the sections taken 24 hours after reperfusion. The peripheral area was less affected, and the outer nuclear cell layer was almost unaffected throughout the observation period. CONCLUSIONS: The proposed method to cause retinal transient ischemia is highly reproducible, and it is easy to simulate the progress and topographical distribution of retinal changes observed in the clinical cases of central retinal arterial occlusion and its subsequent thrombolytic reperfusion. This may provide a useful tool for constructing the effective thrombolytic strategies against the central retinal arterial occlusion and for evaluating the effects of neuroprotective agents.

Animals↗

Ocular effects of adrenomedullin.

The purpose of this study was to determine the expression and effects of adrenomedullin (AM), a novel vasodilator peptide, in the eye. Expression of AM mRNA was examined in the rat iris-ciliary body using reverse transcription-polymerase chain reaction (RT-PCR). In rabbits, intraocular pressure (IOP) was measured periodically after intravitreal injection (20 microl) of AM (10(-7)-10(-4)m) into one eye. In separate groups of rabbits, 30 min after intravitreal injection of either AM-(22-52) (10(-3)m), a specific AM receptor antagonist, or CGRP-(8-37) (10(-3)m), a CGRP1 receptor antagonist, into one eye, AM (10(-6)m) was injected into both eyes, and IOP was measured. Using different rabbits, aqueous protein and cAMP concentrations were determined 6 hr after injection of AM. Expression of AM mRNA was detected in the rat iris-ciliary body. In rabbits, intravitreally administered AM (10(-6)-10(-4)m) profoundly lowered IOP, and the maximum effect was observed at 4-8 h. The ocular hypotensive effect of AM was dose-dependent (10(-7)-10(-4)m). Pretreatment with CGRP-(8-37) did not significantly inhibit the ocular hypotensive effect of AM (10(-6)m), whereas pretreatment with AM-(22-52) completely abolished it. AM (10(-6)m) did not significantly affect aqueous protein concentration. The higher dose of AM (10(-5)m) induced a significant increase in aqueous protein, which was not associated with an increase in the aqueous cAMP content and was significantly inhibited by AM-(22-52) and CGRP-(8-37). These results demonstrate that AM is expressed in the iris-ciliary body and decreases IOP mainly via specific AM receptors, and suggest that AM may play a role in controlling IOP.

Adrenomedullin↗