Bilateral centripetal lipid keratopathy with diffuse anterior scleritis.
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Biomedical subjects
Publications and source records attributed to T Tsuru.
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Incidence of hip fracture among patients with Parkinson's disease (PD) is high, especially in elderly women. To determine effects of various factors on hip fracture risk, we prospectively studied fractures in a cohort of 115 elderly patients of both genders with PD (46 men, 69 women; mean age, 71.9 years) for 1 year. At baseline, we recorded body mass index (BMI), Hoehn and Yahr stage, and postmenopausal interval, and also measured bone mineral density (BMD) and serum concentrations of ionized calcium, intact parathyroid hormone (PTH), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP; a bone resorption marker), and 25-hydroxyvitamin (25-OHD). During the year hip fractures occurred in 18 patients (2 male and 16 female). We compared baseline variables between patients with and without hip fracture. PD patients with decreased BMI, lower BMD, and low concentrations of serum ionized calcium, and 25-OHD (mean 4.0 ng/ml) with compensatory hyperparathyroidsim had increased risk of hip fracture. Female PD patients with long postmenopausal intervals also had increased hip fracture risk. BMI, illness duration, postmenopausal intervals, Hoehn and Yahr stage, 25-OHD, PTH, calcium, and ICTP were determinants of BMD in patients with fracture. Elderly PD patients with low BMI, low BMD, and serum 25-OHD concentrations < or =5 ng/ml with secondary hyperparathyroidism have increased risk of hip fracture, as do female PD patients with long postmenopausal intervals.
PURPOSE: To evaluate risk factors for graft failure and allograft rejection after penetrating keratoplasty (PK). METHODS: We retrospectively studied clinical results of PKs in terms of graft survival and rejection-free graft survival rates. PKs were done on 271 eyes between 1987 and 1997. Clinical results were analyzed by Kaplan-Meier's life table method and the log-rank test. Relative risks and adjusted survival probabilities for each value of the factor were compared with the risk for a specified reference value. RESULTS: The overall rates of graft survival and rejection-free graft survival in 10 years after PK were 79.3% and 77.9%, respectively. Higher relative risk of graft failure was associated with corneal vascularization (relative risk for within one quadrant = 1.67, two quadrants = 2.37, three or more quadrants = 3.39), regraft (relative risk for one failed previously graft = 2.08, two or more failed previously graft = 2.65), aphakia (relative risk = 2.17) or pseudophakia (relative risk = 3.02), presence of anterior synechia (relative risk = 2.91), presence of posterior synechia (relative risk = 2.56), long (more than 85 minutes) operation time (relative risk = 2.20), and older (more than 50 years) recipient age (relative risk = 2.38). Higher relative risk of rejection was associated with corneal vascularization (relative risk for within one quadrant = 2.35, two quadrants = 2.03, three or more quadrants = 2.63), long (more than 85 minutes) operation time (relative risk = 1.47), and younger (less than 60 years) donor age (relative risk = 2.10). There was no association between graft failure or allograft rejection and graft size or suture technique, respectively. CONCLUSION: The risk factors for graft failure after PK were corneal vascularization, regraft, aphakia or pseudophakia, presence of anterior synechia, presence of posterior synechia, long operation time, and older recipient age. The risk factors after PK for allograft rejection were corneal vascularization, long operation time, and younger donor age.
OBJECTIVE: The so-called bone-derived growth factor, beta2-microglobulin, has a regulatory function in bone metabolism by stimulating osteoclast activity. We undertook this study because osteoclast activity is known to be enhanced in patients with immobilized stroke, suggesting that their beta2-microglobulin concentrations may be increased. DESIGN: We studied 79 patients with acute stroke hemiplegia, including 36 men and 43 postmenopausal women ranging in age between 51 and 70 yr. RESULTS: The mean Barthel Index was 43 and 42 for men and women, respectively. The serum beta2-microglobulin concentration was increased in male and female patients, compared with the findings of 44 age-matched control subjects, and the serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen was also increased in male and female patients, compared with the findings of the control subjects. Serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen correlated negatively with Barthel Index scores in both genders, indicating increased bone resorption caused by immobilization in these patients. Linear regression analysis revealed a positive correlation between beta2-microglobulin and pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen in both genders. CONCLUSIONS: These findings suggest that beta2-microglobulin reflects osteoclastic activity in response to stroke-induced immobilization in both genders. Beta2-microglobulin is a useful indicator of bone resorption in patients with immobilized stroke.
Influenza vaccination is strongly recommended for the elderly persons. Especially elderly patients with neurological diseases are at the high risk because they have more tendencies to develop pneumonia than healthy elderly persons. We vaccinated 105 elderly patients with neurological diseases (cerebrovascular disease, Parkinson disease etc.) and 134 people of a control group. Both groups were inoculated with influenza HA vaccine once. The HI titer increase in elderly patients with neurological diseases was equally good enough in the control group and no significant differences was shown in both groups. No severe side effects and adverse reactions were observed in the elderly patient group. This study shows that influenza vaccination is effective and safe for elderly patients with neurological diseases as the well as healthy elderly person and the HI titer increase after a single influenza vaccine injection is expected to be effective to protect influenza infection.
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Truncated polypeptides containing expanded polyglutamine (polyQ) stretches tend to form cytoplasmic or nuclear aggregates in cultured cells, leading to cell death. Although it has been shown recently that caspase-8 coaggregates with polyQ and is activated during polyQ-mediated cell death, little is known of the location and timing of caspase-8 activation by nuclear polyQ aggregates. Also, the relationship between nuclear polyQ aggregate-mediated cell death and activation of other caspases is unclear. In P19 embryonal carcinoma (EC) cells, which can be made to differentiate into neuronal cells, polyQ72 repeats preferentially aggregate in the nucleus. Nuclear aggregates of polyQ72 induced P19 EC cell death, with a high frequency of cells exhibiting morphology characteristic of apoptosis (i.e., roundness, cell shrinkage, chromatin condensation) and DNA fragmentation. In the present study, we used antisera that specifically recognized the active forms of caspase-8, -3, and -9 but not their proforms, and showed that only caspase-8 and -3 were activated during the generation of polyQ72 aggregates in P19 EC cell nuclei. Furthermore, we showed that the caspase inhibitor z-VAD-fmk inhibited DNA fragmentation, but only partially inhibited the appearance of apoptotic morphology. Thus, caspase activation, including caspase-8 and -3, is necessary for polyQ-mediated DNA fragmentation but not sufficient for polyQ-mediated cell death in P19 EC cells.
Inorganic nanofiltration membranes were prepared using silica-zirconia composite sols by the sol-gel method and applied for the permeation experiments of nonaqueous solutions. Pure solvent permeabilities of methanol, ethanol, and 1-propanol were measured at temperatures from 25 to 60 degrees C. For membranes having pore sizes as large as 70 nm, the permeation mechanism of alcohols obeys the viscous flow mechanism irrespective of types of alcohols. On the other hand, the permeation mechanism through porous silica-zirconia membranes having pore diameters of 1 to 5 nm was found to be different from the viscous flow mechanism; small molecules showed larger permeabilities than large molecules. Activation energies of solvent permeability were found to be larger for large molecules and for membranes of smaller pore size. Copyright 2000 Academic Press.
BACKGROUND: The cytokine profiles of specific immunosuppression after anti-adhesion molecule therapy are unknown in a mouse corneal transplantation model. METHODS: Orthotopic mouse corneal transplantation was performed using BALB/c (H-2d) mice as recipients and C3H/He (H-2k) mice as donors. Anti-mouse very late antigen-4 and anti-mouse lymphocyte function-associated antigen-1 monoclonal antibodies (each at a dose of 0.25/mg/day) were administered i.p. until day 7. A second corneal transplantation was performed 5 weeks after the first grafting. Delayed hypersensitivity was tested after the second grafting. Corneal cytokine expression was examined immunohistochemically. The cytokine gene transcription level was assessed in the corneas and splenocytes. RESULTS: All allografts with anti-adhesion molecule therapy survived for 5 weeks. Two weeks after the second grafts in the fellow eye (7 weeks after the first grafts), 50% of the mice with successful grafts bilaterally had low delayed hypersensitivity responses. Low helper T 1 (interferon-gamma and interleukin-2) cytokine gene and protein expression in corneas was observed in monoclonal antibody-treated mice 3 weeks after the first grafting. The mice with successful second grafts showed low corneal T helper 1 cytokine gene and protein expression. High interleukin-4 gene transcription levels in corneas and splenocytes was obtained in both groups in which the grafts were accepted and rejected after the second grafts. CONCLUSIONS: The cytokine profile to differentiate alloantigen-specific acceptance with anti-adhesion therapy to lymphocyte function-associated antigen-1 and very late antigen-4 molecules from rejection after the second grafting is local and systemic low T helper 1 cytokine in corneal transplantation. High interleukin-4 cytokine expression in corneas and splenocytes is not associated with achievement of tolerance induction.
The relation between activation of caspase-8 and polyglutamine aggregates has been focused. We prepared an antiserum (anti-m8D387) that recognizes the active form but not the proform of mouse caspase-8. We used immunostaining with anti-m8D387 antiserum to compare the localizations of activated mcaspase-8 in L929 (clone 1422) cells induced by TNF and polyglutamine aggregates. Anti-m8D387 was positive throughout cytoplasm of the TUNEL-positive cells induced by TNF treatment, whereas the anti-m8D387 reactivity was not positive throughout cytoplasm of the cells expressing polyglutamine but was restricted to polyglutamine aggregates. In contrast with TNF-treated cells, cells expressing anti-m8D387-positive cytoplasmic polyglutamine aggregates did not undergo TUNEL-positive apoptosis. Thus activated caspase-8 associated with polyglutamine aggregates alone was not sufficient to induce TUNEL-positive apoptosis of L929 (clone 1422) cells. The distribution of activated caspase-8 associated with polyglutamine aggregates may be essential for the polyglutamine-mediated cell death or downstream of caspase-8 may be different in the TNF-treated cells and cells expressing polyglutamine.
To determine whether preservation of the donor cornea prevents allograft rejection, orthotopic corneal transplantation was performed using corneas preserved in storage medium (Optisol-GS((R))). Donor corneas harvested from C3H/He (H-2(k)) mice and B10.D2 (H-2(d)) mice were preserved in storage medium for 0, 3, 7 and 14 days, and then transplanted into the corneal beds of the recipient BALB/c (H-2(d)) mice. Graft survival was determined clinically and histologically. The expression of major histocompatibility complex (MHC) molecules in the preserved corneas was analysed by immunohistochemistry and Western blotting. Donor-specific cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses were assessed 3 weeks after grafting. Active suppression of DTH in the recipient mice was also examined 3 weeks after grafting. The survival of 14 day preserved allografts was significantly higher than that of the non-preserved allografts in both MHC and minor histocompatibility (H) antigens, and minor H only disparate combination. The recipients of the preserved allografts failed to induce both CTL and DTH. The active suppression of DTH was not acquired in these recipients. The expression of donor-derived MHC class I antigens was markedly reduced in the corneas after preservation. Preservation of the donor cornea had a remarkable effect on the prevention of corneal allograft rejection. Since the preserved allografts failed to induce donor-specific CTL and DTH, and active suppression of DTH was not acquired in the recipients, the prevention of allo-rejection is due to a failure of allo-sensitization. These results indicate that the reduction of MHC class I antigens and minor H antigens expression in the preserved grafts induces a failure of allo-sensitization and leads to the high rate of acceptance in corneal allografts.
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We report here a case involving a 14-year-old boy who developed acute disseminated encephalomyelitis following live rubella vaccination. The patient became febrile and began to experience nuchal pain 16 days after the immunization. By 22 days after immunization, he experienced difficulty in walking. By 24 days, he had developed tetraparesis with retention of urine, and total sensory loss below the Th1 dermatomal level. He was febrile at this point and showed nuchal rigidity and Lhermitte's sign. Cerebrospinal fluid examination revealed elevated cell counts, protein level, and myelin basic protein. T2-weighted magnetic resonance imaging detected high intensity lesions in the bilateral cerebral white matter and cervical spinal cord. Following the administration of intravenous corticosteroids, the patient's clinical symptoms improved rapidly.
PURPOSE: To investigate the effect of anti-inflammatory agents on conjunctival inflammation and corneal haze formation after excimer laser keratectomy. SETTING: Department of Ophthalmology, University of Tokyo Faculty of Medicine, Tokyo, Japan. METHODS: After excimer laser keratectomy was performed in 21 rabbits (42 eyes), saline, betamethasone 0.1%, or diclofenac 0.1% was topically applied 6 times a day for 4 weeks and then 3 times a day for 8 weeks. The degree of conjunctival inflammation was determined 1, 2, 3, and 7 days after the keratectomy. The degree of corneal haze was quantitatively measured using a digital analyzer before and once a week after the keratectomy. The expression of type IV collagen in the corneas at baseline and 4 and 12 weeks after the keratectomy was examined immunohistochemically. RESULTS: Compared with saline, betamethasone and diclofenac significantly decreased early-phase conjunctival inflammation. Betamethasone significantly inhibited corneal haze formation compared with saline at 3 to 5 and 8 to 12 weeks. Diclofenac did not inhibit corneal haze formation significantly. Although betamethasone tended to be more effective in inhibiting corneal haze formation and deposition of type IV collagen than diclofenac, there was no statistical difference between the 2 anti-inflammatory agents. CONCLUSION: Topically applied betamethasone effectively suppressed corneal haze formation after excimer laser keratectomy. Diclofenac was not statistically effective in inhibiting corneal haze formation.
Two children with Landau-Kleffner syndrome were successfully treated with antiepileptic drugs and a high-dose intravenous corticosteroid. A combination of valproate and a benzodiazepine (clonazepam or diazepam) ameliorated epileptic seizures and electroencephalographic spikes and waves, but speech disturbances persisted. Both patients were treated with an intravenous infusion of high-dose methylprednisolone sodium succinate (20 mg/kg daily) for 3 consecutive days. This infusion was repeated three times with a 4-day interval between treatments, which resulted in a rapid improvement in speech ability. After intravenous therapy, prednisolone was given orally (2 mg/kg daily for 1 month, then gradually withdrawn), which maintained the clinical improvement in speech.
PURPOSE: To assess the effects of histocompatibility Y (H-Y) antigen matching on the rate of corneal allograft rejection after penetrating keratoplasty (PKP). METHODS: We retrospectively investigated the graft survival rate and rejection-free graft survival rate after PKP in 396 eyes. The compatible combinations of H-Y antigen included male donors and male recipients (n = 135), female donors and male recipients (n = 107), and female donors and female recipients (n = 60). Incompatible combination was from male donors and female recipients (n = 94). The eyes were classified into two groups--high-risk (168 eyes) and low-risk (228 eyes)--depending on the degree of vascularisation in the recipient corneas or a history of previous allograft rejection. Data were analysed using the Kaplan-Meier life table method, the log-rank test and the Cox proportional hazards model. RESULTS: In both the high-risk and low-risk groups, the graft survival and rejection-free graft survival rates were not affected by the H-Y compatibility. The graft survival (p < 0.001) and rejection-free graft survival (p < 0.001) rates were higher in the low-risk group than in the high-risk group. High-risk PKP was associated with greater risk of graft failure (risk ratio, 2.33) and rejection (risk ratio, 2.05) than low-risk PKP. CONCLUSION: H-Y antigen matching does not influence the rate of allograft rejection after PKP.
PURPOSE: To determine whether cholestanol induces cornea endothelial and lens epithelial cell death in vitro. METHODS: Cornea endothelial and lens epithelial cells were cultured in minimum essential media with 10% fetal bovine serum containing 10 microg/ml cholesterol in ethanol, 10 microg/ml cholestanol in ethanol, or 1% ethanol. These cells, stained using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) method, were analyzed by laser cytometer. The activities of ICE and CPP32 proteases in cells were also measured. RESULTS: Both cornea endothelial and lens epithelial cells cultured with 10 microg/ml cholestanol showed a significant loss of viability. The nuclei of these cells cultured with 10 microg/ml cholestanol were more frequently stained than those exposed to 10 microg/ml cholesterol or 1% ethanol. Quantitative analysis of apoptotic DNA fragmentation confirmed that the cholestanol induced apoptosis of these cells in a time-dependent manner. The activities of interleukin-1beta-converting enzyme (ICE) and CPP32 proteases for cells cultured with 10 microg/ml cholestanol were significantly higher than those observed in control cells. CONCLUSIONS: In vitro, cholestanol was taken up by corneal endothelial cells and lens epithelial cells, an event that led to apoptosis of these cells.
BACKGROUND: Anti-alphabeta T cell receptor monoclonal antibody (R73) has been reported to be a potent immunosuppressant. The suppressive effects of this antibody on allograft rejection after corneal transplantation are unknown. METHODS: Orthotopic rat penetrating keratoplasty was performed using Lewis rats as recipients and Brown Norway and Fisher rats as donors. The treated groups received R73 intraperitoneally until day 12 after the transplantation. In grafted rats with or without R73 treatment, cytokine expression of the aqueous humor, corneal-infiltrating cells, draining lymph nodes, and splenocytes was determined. Delayed-type hypersensitivity (DTH) responses were compared. RESULTS: All allografts in the untreated controls of Fisher-to-Lewis or BN-to-Lewis rat combinations were rejected within 14 days. In contrast, indefinite survival rates of the postoperative R73-treated group increased to 86% in the Fisher-to-Lewis and 23% in the Brown Norway-to-Lewis combinations, respectively. Interferon-y, interleukin (IL)-2 (T helper [Th]1), and IL-10 (Th2), but not IL-4 (Th2), expression of the eye and DTH responses in the control group were suppressed in the R73-treated group. Both IL-2 and IL-10 expression after mixed lymphocyte culture in the R73-treated group were significantly lower than those of the naive and untreated control group. CONCLUSIONS: alphabeta T cell receptor-targeted therapy prevents allograft rejection in rat corneal transplantation as evidenced by suppression of DTH responses. The cytokine profile after R73 treatment was characterized by low interferon-gamma, IL-2, and IL-10, and high IL-4 expression.