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Biomedical subjects

S Kusaka

Publications and source records attributed to S Kusaka.

At least 19 recordsLinked to original sources

Intravitreal injection of bevacizumab for choroidal neovascularisation associated with pathological myopia.

AIM: To assess the efficacy and safety of an intravitreal injection of bevacizumab (Avastin(R)) for myopic choroidal neovascularisation (mCNV). METHODS: Intravitreal bevacizumab (1 mg) was injected into eight eyes of eight patients with mCNV in this non-randomised, interventional case series. The best-corrected visual acuity (BCVA) was measured and the optical coherence tomography (OCT) and fluorescein angiography findings were examined before and after treatment. The minimum follow-up time was 3 months. RESULTS: The mean BCVA was 0.26 before treatment and 0.51 at the last visit (p = 0.009). The BCVA improved to two or more lines in six eyes (75%) and remained the same in two eyes (25%). Leakage from the mCNV on fluorescein angiography decreased in seven eyes (87.5%). The choroidal neovascularisation area on fluorescein angiography (p = 0.049) and the foveal thickness on OCT images decreased significantly (p = 0.027) after the treatment. No major complications developed. CONCLUSION: Intravitreal injection of bevacizumab seems to be an effective and safe treatment for mCNV.

Adult↗

Donor-derived small cell lung carcinoma in a kidney transplant recipient.

BACKGROUND: Transplantation of donor-derived malignancies during organ transplantation fortunately is very rare. Discontinuation of immunosuppressive medications under these circumstances has previously resulted in complete tumor rejection. Ectopic adrenocorticotropic hormone (ACTH) production may result in Cushing syndrome and is not an uncommon paraneoplastic feature of small cell carcinoma of the lung. Theoretically, in the organ transplantation setting, the resulting high cortisol levels could suppress a tumor-rejection immune response. However, to the authors' knowledge, no such clinical scenario has been described in the literature published to date. METHODS: A 25-year-old living related kidney transplant recipient presented with Cushing syndrome 32 months after transplantation. The donor had been diagnosed with small cell carcinoma of the lung 22 months earlier. On further evaluation, the kidney recipient was diagnosed with donor-derived small cell lung carcinoma of the transplanted kidney. She was found to have extensive disease involving the liver and retroperitoneum. Despite discontinuation of immunosuppressive medications, the disease progressed and cortisol levels remained elevated during 6 weeks of observation. RESULTS: The patient received six cycles of cisplatin and etoposide, which resulted in resolution of her hypercortisolemia and a complete remission of her donor-derived small cell carcinoma. At last follow-up, she was 12 months from completing her therapy and continued in complete remission. CONCLUSIONS: Donor-derived small cell carcinoma and ectopic ACTH production can occur in a patient after kidney transplantation.

Adrenocorticotropic Hormone↗

Functional Kir7.1 channels localized at the root of apical processes in rat retinal pigment epithelium.

1. The inwardly rectifying K+ channel current (IK(IR)) recorded from isolated retinal pigmented epithelial (RPE) cells showed poor dependence on external K+ ([K+]o) and low sensitivity to block by Ba2+. We examined the molecular identity and specific subcellular localization of the KIR channel in RPE cells. 2. The Kir7.1 channel current heterologously expressed in HEK293T cells (human embryonic kidney cell line) showed identical properties to those of the RPE IK(IR), i.e. poor dependence on [K+]o and low sensitivity to Ba2+ block. 3. Expression of Kir7.1 mRNA and protein was detected in RPE cells by RT-PCR and immunoblot techniques, respectively. 4. Immunohistochemical studies including electron microscopy revealed that the Kir7.1 channel was localized specifically at the proximal roots of the apical processes of RPE cells, where Na+,K+-ATPase immunoreactivity was also detected. 5. The middle-distal portions of apical processes of RPE cells in the intact tissue exhibited immunoreactivity of Kir4.1, a common KIR channel. In the isolated RPE cells, however, Kir4.1 immunoreactivity was largely lost, while Kir7.1 immunoreactivity remained. 6. These data indicate that the only IK(IR) recorded in isolated RPE cells is derived from the functional Kir7.1 channel localized at the root of apical processes. Co-localization with Na+,K+-ATPase suggests that the Kir7.1 channel may provide the pathway for recycling of K+ to maintain pump activity and thus is essential for K+ handling in RPE cells.

Amino Acid Sequence↗

Topographic analysis of astigmatism induced by scleral shortening in pig eyes.

BACKGROUND: Corneal astigmatism is a severe postoperative problem in foveal translocation surgery. We evaluated the corneal astigmatism induced by scleral shortening in pig eyes in vitro. METHODS: We created three sizes of scleral shortening in pig eyes and examined the preoperative and postoperative corneal astigmatism. The three sizes of scleral shortening were; 6 mm x 12 mm, 9 mm x 12 mm, and 6 mm x 16 mm (radial x circumferential). The shortenings were created 11 mm from the limbus with 10 eyes in each group. Videokeratographic measurements were performed using the CAS System 2000, preoperatively and postoperatively, and the astigmatism caused by the scleral shortening was evaluated. RESULTS: The surgically-induced astigmatism was 2.1 +/- 1.2 diopters (D) in the 6 mm x 12 mm group, 5.2+/-1.5 D in the 9 mm x 12 mm group, and 3.7+/-1.0 D in the 6 mm x 16 mm group. Corneal astigmatism caused by scleral shortening depended on both the radial and circumferential shortening. Pre- and postoperative topographic corneal maps showed an irregular astigmatism pattern (lazy bowtie pattern). Because the central zone of the cornea showed a relatively regular astigmatism, the corneal astigmatism induced by scleral shortening did not affect the predicted corneal acuity. CONCLUSIONS: In foveal translocation surgery with scleral shortening, an excessive scleral resection in the radial direction can cause clinically intolerable regular and irregular astigmatism. Minimal scleral shortening that will satisfy the required translocated distance is recommended to reduce the risk/benefit ratio.

Animals↗

Visual function after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy.

PURPOSE: To assess functional and anatomical outcomes after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy. METHODS: Foveal translocation with 360-degree retinotomy was performed in 11 eyes of 11 patients with myopic neovascular maculopathy. Ten eyes had simultaneous torsional muscle surgery with recession of the superior oblique muscle and tucking of the inferior oblique muscle. Silicone oil removal with or without intraocular lens implantation was performed 2 to 8 weeks after the primary procedure. Visual acuity, binocular function, and degree of cyclotorsion were assessed preoperatively and postoperatively. Angles of retinal and globe rotation, distance of foveal shift, and surgical complications were also investigated. RESULTS: With a mean postoperative follow-up of 6.2 months (range, 3 to 13 months), vision improved (greater than 0.2 logarithm of minimal angle of resolution [logMAR] units) in eight eyes, was unchanged in two eyes, and worsened (greater than 0.2 logMAR units) in 1 eye. Seven of 11 eyes (64%) had a final visual acuity of 20/50 or better. Five patients developed or maintained binocular fusion, four patients continued to have suppression, and two patients developed diplopia that was managed by spectacles with Fresnel prisms. Subjective cyclotorsion was less than 8 degrees in 10 eyes. Mean retinal and globe rotations were 23.4 degrees and 19.8 degrees, respectively. Average size of the choroidal neovascular membrane was 0.8 disk diameter, whereas the average distance of foveal shift was 1.5 disk diameter. After the primary procedure, three eyes developed retinal detachment, one eye macular hole, and one eye proliferative vitreoretinopathy. These complications were successfully managed by additional surgery. CONCLUSION: Foveal translocation with 360-degree retinotomy is effective in restoring vision in some patients with myopic neovascular maculopathy. Although the development of torsional diplopia is generally obviated by simultaneous extraocular muscle surgery, a relatively high incidence of surgical complications should be taken into account with this procedure.

Aged↗

Indocyanine green facilitates removal of epiretinal and internal limiting membranes in myopic eyes with retinal detachment.

PURPOSE: To describe the use of intravitreal indocyanine green as an aid to identifying epiretinal membranes and internal-limiting membranes during surgery for a retinal detachment resulting from a macular hole. METHODS: A 62-year-old man who had a retinal detachment resulting from a macular hole underwent vitrectomy. During the surgery, intravitreal indocyanine green was injected intravitreally. RESULTS: The internal-limiting membrane was stained green, but the epiretinal membrane was unstained. Because the epiretinal membrane and internal-limiting membrane were clearly identified, they could be completely removed. The clinical observations of the epiretinal membrane and internal-limiting membrane excised were confirmed by electron microscopy. Successful reattachment was obtained without damage to the retina. CONCLUSION: Removal of epiretinal membrane and internal-limiting membrane can be facilitated by using intravitreal indocyanine green during vitrectomy. We recommend further studies to confirm the benefit of this technique.

Basement Membrane↗

Effect of Ca(2+)-free and Mg(2+)-free BSS Plus solution on the retinal pigment epithelium and retina in rabbits.

PURPOSE: To determine whether intravitreal irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus (Alcon Laboratory, Fort Worth, Texas) solution alters the adhesiveness between the retinal pigment epithelium and the retina of rabbits. METHODS: Thirty-four eyes of 34 Dutch pigmented rabbits underwent lensectomy and vitrectomy. Subsequently, the vitreous cavity of 24 eyes was irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 10 or 20 minutes. The other 10 eyes were irrigated with BSS Plus solution for 20 minutes as controls. To determine the adhesiveness between the retinal pigment epithelium and retina, a retinal detachment was produced in 12 of the 34 eyes. The apical surface of the retinal pigment epithelium and the photoreceptor outer segments were examined by scanning electron microscopy. Retinal physiology was assessed by electroretinography and retinal morphology by light microscopy. RESULTS: After retinal detachment was produced, the number of cone sheaths on the apical surface of the retinal pigment epithelium after irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes (33 +/- 15, mean +/- SD) was significantly less than the number of cone sheaths on the apical surface of the retinal pigment epithelium of eyes after irrigation with BSS Plus solution for 20 minutes (120 +/- 50) or the number of cone sheaths on the apical surface of the retinal pigment epithelium of eyes after 10 minutes of irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution (115 +/- 49; P =.02). The b-wave amplitudes in the eyes irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes were depressed compared with the b-waves in eyes irrigated with BSS Plus solution for 20 minutes on the first postoperative day (P =.03). After the third postoperative day, there was no significant difference in the b-waves (P >.06). Light microscopy demonstrated no morphologic abnormalities after the use of both solutions. CONCLUSIONS: Intravitreal irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes altered the adhesion between the retinal pigment epithelium microvilli and retinal outer segments and made the creation of retinal detachment less traumatic. These results suggest that Ca(2+)-free and Mg(2+)-free BSS Plus solution may be of clinical value for the creation of an intentional retinal detachment for foveal translocation surgery.

Animals↗

Assessment of nuclear sclerosis after nonvitrectomizing vitreous surgery.

PURPOSE: Nuclear sclerosis develops frequently after successful pars plana vitrectomy. We evaluated changes in the degree of nuclear sclerosis after nonvitrectomizing vitreous surgery for idiopathic epimacular proliferation. METHODS: Forty-one consecutive patients (41 eyes) underwent removal of idiopathic epimacular proliferation by nonvitrectomizing vitreous surgery and were followed postoperatively for at least 12 months. Visual acuity, refractive error, slit-lamp biomicroscopy, and Scheimpflug photographs were assessed preoperatively and postoperatively to evaluate changes in the degree of lenticular opacification. Quantitative analysis of the nuclear sclerosis was performed by densitometry with Scheimpflug photographs performed on only the last 21 patients. We evaluated these measurements by comparing statistically the preoperative and postoperative difference between both eyes (operative eye minus nonoperative ocular data). RESULTS: There was no significant difference in the progression of nuclear sclerosis or degree of myopic shift between the operated and fellow eyes during postoperative follow-up (mean +/- SD, 22 +/- 8 months; median, 22 months; range, 12 to 48 months). The average preoperative and postoperative refractive errors in operated eyes were 0.0 +/- 2.4 diopters and 0.1 +/- 2.5 diopters, respectively; the average difference in the refractive errors between both eyes was -0.2 +/- 0.7 diopter preoperatively and -0.2 +/- 0.9 diopter postoperatively (P =.961, paired t test). The average preoperative and postoperative nuclear density values by Scheimpflug photography in 21 operated eyes were, respectively, 72 +/- 18 nuclear density units and 75 +/- 17 nuclear density units; the average difference in nuclear density values between both eyes was -1 +/- 4 nuclear density units preoperatively and 0 +/- 6 nuclear density units postoperatively (P =.631, paired t test). CONCLUSION: Progression of nuclear sclerotic cataract based on changes in refractive error and Scheimpflug photography was not observed after nonvitrectomizing vitreous surgery.

Aged↗

Evaluation of the peripheral visual field after foveal translocation.

PURPOSE: To evaluate the peripheral visual field after foveal translocation with scleral imbrication or 360-degree retinotomy. METHODS: Retrospective, single-center, nonrandomized study. We calculated the rate of preservation of the peripheral visual field using Goldmann perimetry by dividing the width of the postoperative V-4 isopter by the preoperative width and expressing the result as a percentage. RESULTS: In nine eyes that underwent scleral imbrication, the rate of preservation was 100.0% superiorly, 102.6% superotemporally, 99.9% temporally, 97.9% inferotemporally, 96.9% inferiorly, 82.3% inferonasally, 93.7% nasally, and 87.3% superonasally. In 33 eyes that underwent 360-degree retinotomy, it was 89.1%, 87.0%, 81.9%, 78.1%, 86.6%, 90.0%, 89.9%, and 86.8%, respectively. CONCLUSION: After foveal translocation with scleral imbrication, the peripheral visual field was preserved except for slight narrowing nasally; 360-degree retinotomy resulted in preservation of the visual field, except for slight narrowing in all meridians.

Aged↗

Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration.

PURPOSE: To report the results of three methods of foveal translocation in the presence of subfoveal choroidal neovascular membrane resulting from age-related macular degeneration. METHODS: We treated 51 eyes of 51 consecutive patients with subfoveal choroidal neovascular membranes resulting from age-related macular degeneration with one of three techniques of foveal translocation surgery: foveal translocation with partial retinotomy (n = 6), limited translocation (n = 9), and translocation with 360-degree retinotomy (n = 36). All patients were followed for at least 6 months postoperatively. The size of the choroidal neovascular membrane and the amount of foveal displacement, the best-corrected visual acuity, and complications were recorded preoperatively and postoperatively. RESULTS: The mean distance of the foveal translocation was greater in the 360-degree retinotomy group (3340 microm) than in the partial retinotomy (1060 microm, P <.001) and the limited translocation groups (1120 microm, P <.001). A final visual acuity of 20/200 or better was achieved in two eyes (33%) in the partial retinotomy group, seven eyes (78%) in the limited translocation group, and 23 eyes (64%) in the 360-degree retinotomy group. The final visual acuity improved by 0.2 logarithm of minimal angle of resolution (logMAR) unit or more in one eye (17%), one eye (11%), and seven eyes (19%), respectively. The final visual acuity was maintained within 1 line in zero eyes, five eyes (56%), and 19 eyes (53%), respectively. A retinal detachment developed postoperatively in five eyes (83%), zero eyes (0%), and 15 eyes (42%), respectively. CONCLUSIONS: A significant number of patients improved or maintained best-corrected visual acuity after translocation with 360-degree retinotomy, and limited translocation, whereas translocation with 360-degree retinotomy is suitable for larger choroidal neovascular membranes because it resulted in the greatest foveal displacement among the three translocation procedures.

Aged↗

Clonotype analysis of human alloreactive T cells: a novel approach to studying peripheral tolerance in a transplant recipient.

The recognition of allo-MHC and associated peptides on the surface of graft-derived APC by host T cells (direct pathway allorecognition) plays an important role in acute rejection after organ transplantation. However, the status of the direct pathway T cells in stable long term transplants remains unclear. To detect alloreactive T cell clones in PBL and the allograft during the transplant tolerance, we utilized RT-PCR instead of functional assays, which tend to underestimate their in vivo frequencies. We established alloreactive CD4+ and CD8+ T cell clones from peripheral blood sampled during the stable tolerance phase of a patient whose graft maintained good function for 9 years, 7 without immunosuppression. We analyzed the sequence of TCR Vbeta and Valpha genes and made clonotype-specific probes that allowed us to detect each clone in peripheral blood or biopsy specimens obtained during a 1-year period before and after the rapid onset of chronic rejection. We found an unexpectedly high level of donor HLA-specific T cell clonotype mRNA in peripheral blood during the late tolerance phase. Strong signals for two CD4+ clonotypes were detected in association with focal T cell infiltrates in the biopsy. Chronic rejection was associated with a reduction in direct pathway T cell clonotype mRNA in peripheral blood and the graft. Our data are inconsistent with the hypothesis that direct pathway T cells are involved only in early acute rejection events and suggest the possibility that some such T cells may contribute to the maintenance of peripheral tolerance to an allograft.

Amino Acid Sequence↗

X-linked retinoschisis with point mutations in the XLRS1 gene.

BACKGROUND: X-linked retinoschisis (XLRS) is a relatively rare vitreoretinal dystrophy that causes visual loss in young men. Recently, a gene responsible for this disease, designated XLRS1, was identified, and several deleterious gene mutations were reported. OBJECTIVE: To analyze Japanese patients clinically diagnosed as having XLRS formutational changes in the XLRS1 gene. METHODS: Ten patients with XLRS underwent full ophthalmologic examination, including slitlamp biomicroscopy and dilated funduscopy. Genomic DNA was isolated from leukocytes, and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. RESULTS: Point mutations in the XLRS1 gene were identified in all 10 patients. The mutations were identical in each of 2 pairs of brothers. Six of the point mutations represented missense mutations, 1 was a nonsense mutation, and 1 was a frameshift mutation. Five of the mutations are newly reported herein. CONCLUSIONS: The discovery of new point mutations in this study increases the available information regarding the spectrum of genetic abnormalities and clinical manifestations of XLRS. However, the limited data failed to reveal a correlation between mutation and disease phenotype. CLINICAL RELEVANCE: Identification of mutations in the XLRS1 gene and expanded information on clinical manifestations will facilitate early diagnosis, appropriate early therapy, and genetic counseling regarding the prognosis of XLRS.

Adolescent↗

Amsler grid examination and optical coherence tomography of a macular hole caused by accidental Nd:YAG laser injury.

PURPOSE: To compare a macular hole from accidental Nd:YAG laser injury with idiopathic macular holes. METHODS: Case report. In a 24-year-old man with accidental Nd:YAG laser injury, right eye, Amsler grid testing and optical coherence tomography were performed. RESULTS: Nd:YAG laser injury was responsible for a macular hole about 700 microm in diameter. The visual acuity was 20/100. Amsler grid testing displayed a central scotoma with no surrounding distortion. Optical coherence tomography showed a defect in all retinal layers at the macula. CONCLUSION: The scotoma caused by Nd:YAG laser injury is not surrounded by distortion; the hole is produced by the defect of all retinal layers. In contrast, idiopathic macular holes generally produce a pincushion pattern on Amsler grid testing and have no tissue loss.

Accidents, Occupational↗

Loss of tolerance to a maternal kidney transplant is selective for HLA class II: evidence from trans-vivo DTH and alloantibody analysis.

We studied late graft rejection in a patient who had received a kidney transplant 9-10 years earlier from his mother and who had been off all immunosuppressive drugs for 7 years at the time of graft rejection onset. The mother differed for one HLA-A (A3) and one HLA-B (B62) antigen but had only a subtype mismatch at the HLA-DR beta 1 locus (donor: DR beta 1*1104; recipient: DR beta 1*1102). A gradual rise in serum creatinine from 1.8 to 2.0 mg/dl at year 9 prompted a biopsy, which was negative for rejection (focal infiltrates but no tubulitis). Ten months later the patient's creatinine had risen to > 3.4 mg/dl, and a second biopsy revealed extensive tubulitis, cellular rejection, and glomerular sclerosis. Sonicates of donor leukocytes triggered no delayed-type hypersensitivity (DTH) response above background (PBMC only) in the patient's peripheral blood leukocytes obtained prior to year 9. A gradual recovery of antidonor DTH response between year 9 and 10 closely paralleled the change from tolerant to rejection status. Antidonor antibody was also undetectable in serum prior to year 9, but a donor-reactive antibody did develop at year 10.2 shortly after the peak of DTH response. The serum level of soluble donor HLA class I B62 antigen rose > 10-fold over prerejection level at the time of the biopsy-proven rejection, suggesting a possible trigger for both the cellular and humoral immune response. Nonetheless, we found no evidence for the development of humoral or cellular immunity to maternal HLA class I. Instead, DTH analysis of memory T cells of the patient obtained after rejection showed that a single maternal HLA DR beta 1*1104 allopeptide, differing by two amino acids in sequence from the peptide of the recipient (DR beta 1*1102), stimulated a strong memory DTH response. Similarly, we found an anti-HLA class II donor-specific antibody in serum that appeared to be crossreactive with DR beta 1*1104 and DR beta 1*1101 but not with the recipient DR beta 1*1102 antigen. The data support the idea of a profound unresponsive state at both the cellular (DTH) and humoral level toward maternal HLA class I antigens that was not reversed even during late cellular rejection, despite the release of high levels of soluble HLA class I. Furthermore, the data suggest that DTH recovery was a close correlate of the onset of rejection and this "indirect" alloresponse, like the anti-donor alloantibody response that followed, was directed not to noninherited maternal HLA-A,B antigens but to the maternal HLA DR beta 1*1104 subtype.

Adolescent↗

Human allograft acceptance is associated with immune regulation.

The ultimate goal of transplantation is drug-free allograft acceptance, which is rarely encountered in transplant recipients. Using a novel human-to-mouse "trans vivo" delayed-type hypersensitivity assay, we assessed donor-reactive cell-mediated immune responses in kidney and liver transplant patients, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the others (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded strongly to recall, but not donor, antigens. Furthermore, when donor and recall antigens were colocalized, the recall response in these three patients was inhibited. This donor antigen-linked nonresponsiveness was observed in four other patients who are still maintained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relies on either TGF-beta or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immune regulation pattern, which may be useful in the diagnosis and/or monitoring of transplant patients for allograft acceptance.

Animals↗