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Biomedical subjects

R Manabe

Publications and source records attributed to R Manabe.

At least 55 records · Page 3Linked to original sources

Co-localization of adrenergic receptors and vitamin-D-dependent calcium-binding protein (calbindin) in the dopaminergic amacrine cells of the rat retina.

Using antisera against tyrosine hydroxylase (TH) and purified beta 2-adrenergic receptors (beta 2-AdR), we found that TH- and AdR-like immunoreactivities coexisted in large amacrine cells. These findings indicated an association between dopamine-containing amacrine cells and adrenergic amacrine cells. The present study also showed that amacrine cells with TH-like immunoreactivity have vitamin-D-dependent calcium-binding protein (calbindin, 27,000 kDa)-like immunoreactivity as well, suggesting that calbindin plays an important postsynaptic role in dopaminergic amacrine cells.

Animals↗

Intraocular penetration of CT-112, an aldose reductase inhibitor, following topical instillation.

Intraocular penetration of 5-(3-ethoxy-4-pentyloxyphenyl)thiazolidine-2,4-dione (CT-112), an aldose reductase inhibitor, was investigated in rabbits following topical instillation. The concentration of CT-112 in corneal epithelium, stroma, endothelium, lens, and aqueous humor, was sequentially determined by high-performance liquid chromatography. CT-112 peaked in the corneal epithelium, stroma, endothelium and aqueous humor in 30 minutes following instillation, then gradually diminished time-dependently over a period of 24 hours. CT-112 remained detectable in the lens up to 24 hours, with a peak concentration at 2 hours after instillation.

Administration, Topical↗

A case of simultaneous bilateral herpetic epithelial keratitis.

The patient, a 56-year-old man, presented with dendritic keratitis in the right eye and geographic keratitis in the left, with decreased corneal sensation in both eyes. The virus isolated from both eyes was identified as herpes simplex virus (HSV-1) by the indirect immunofluorescent method using anti-HSV-1 monoclonal antibody. Antibody tests of paired sera suggested that the epithelial lesions were not primary but recurrent. No significant difference was observed in DNA cleavage patterns between the virus isolates obtained bilaterally.

Cell Division↗

Comparative efficacy of three antiviral drugs in mice herpetic keratitis.

The antiherpetic effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in vitro and in vivo were investigated in comparison with those of acyclovir (ACV) and 5-iodo-2'-deoxyuridine (IDU). ACV was found to be consistently superior to the other two agents in antiviral activity against all ocular isolates in vitro. In vivo tests in mice, in contrast, showed DHPG in ointment form to be more effective than ACV in treating herpetic keratitis. It was noted that even 0.03% DHPG ointment was as efficacious as 0.3% ACV ointment. Other studies using the same keratitis model also demonstrated that DHPG eyedrop solution is far more effective than IDU eyedrop solution. These results indicate that DHPG can be a useful antiviral agent in the treatment of herpetic keratitis.

Acyclovir↗

[Penetrating keratoplasty and cataract surgery].

Of 46 eyes undergoing simultaneous penetrating keratoplasty and cataract extraction, 25 grafts (54%) remained clear with an average follow-up of 37 months. This low success rate can be party explained by the fact that more than 50% of our patients had unfavourable ocular conditions preoperatively. In case of simultaneous procedures, methods of cataract extraction (ICCE or ECCE) did not have any significant affect on the rate of clear grafts. In eyes with favourable ocular conditions preoperatively, the rates of clear grafts were similar (approximately 75%) in cases of simultaneous operation (21 eyes) and separate operation (8 eyes).

Adult↗

Differential regulation of fibronectin synthesis in three different types of corneal cells.

The production of fibronectin (FN) and its response to serum or epidermal growth factor (EGF) were investigated in three different types of rabbit corneal cells cultured in vitro. The corneal epithelial cells, stromal fibroblasts (keratocytes) and endothelial cells were separately cultured in different media: basic medium containing minimal serum (0.5%), basic medium with supplementary serum at a final concentration of 10% and basic medium with 100 ng/ml EGF, respectively. FN production by each type of cell was examined either by the immunofluorescent staining method or by the metabolic labeling method followed by immunoprecipitation of FN in the culture medium. Each type of corneal cell produced and secreted FN. FN secretion into the culture medium by keratocytes and by endothelial cells was enhanced by the addition of EGF. However, FN secretion by epithelial cells was lowered by the additional serum or EGF. Furthermore, when the epithelial cells were cultured in the basic medium, DNA synthesis was low but FN secretion was high. These results suggest that the control mechanism of FN production differs between epithelial cells and keratocytes or endothelial cells.

Animals↗

Presence of epidermal growth factor in human tears.

Epidermal growth factor (EGF) is a polypeptide that stimulates the growth of various tissues, including the cornea. The presence of EGF in tears from normal volunteers and in aqueous humor from cataract patients was investigated via human EGF (hEGF)-specific radioimmunoassay. Immunoreactive hEGF was found to be present at similar concentrations in both reflex (ranging from 0.7 to 8.1 ng/ml) and non-reflex tears (ranging from 1.9 to 9.7 ng/ml), but was undetectable in aqueous humor. Immunoreactive EGF in human tears was indistinguishable immunologically, biologically and biochemically from urine EGF and standard hEGF.

Adult↗

Vitamin A eyedrops for superior limbic keratoconjunctivitis.

We treated 12 patients with superior limbic keratoconjunctivitis with topical vitamin A (retinol palmitate) eyedrops. After a follow-up period of at least three months, this therapy was found to be effective, to a varying extent, in ten patients (83%). Superior limbic keratoconjunctivitis lesions did not recur in these patients as long as topical application was continued.

Adult↗

Aldose reductase inhibitor (CT-112) eyedrops for diabetic corneal epitheliopathy.

We treated two diabetic patients with corneal epithelial disorder that resisted conventional medical therapy with topical CT-112 (5-[3-ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione), a newly synthesized aldose reductase inhibitor. One patient had developed recurrent corneal erosion after vitrectomy and the other had spontaneously developed superficial punctate keratopathy. The corneal lesion in each patient responded to topical CT-112 in two to four weeks and was almost cleared within two months. A similar corneal lesion recurred in both patients soon after CT-112 was discontinued, but it disappeared again when the drug was resumed.

Aged↗

Histamine H1-receptor in the retina: species differences.

Histamine H1-receptors in membranes of the various mammalian retinas were studied by [3H]mepyramine binding assay. Specific [3H]mepyramine bindings to bovine, pig, dog and human retinas were observed with the dissociation constants (KD), 3.8 +/- 1.2 nM, 1.8 +/- 0.6 nM, 2.6 +/- 0.6 nM and 3.0 +/- 0.9 nM, respectively, which were similar to those found in brains. But there was no detectable specific binding in the guinea-pig and rabbit retinas. The number of binding sites (Bmax) ranged from negligible value to 290.7 +/- 51.7 fmole/mg protein(human retina). Some H1-antagonists acted as potent agents in competing with [3H]mepyramine binding to bovine and pig retinas. These results indicated that histamine H1-receptors exist in some mammalian retina and have similar characteristics to those in brain membranes, but they distributes in the wide difference of the binding capacities among the species, while in brain variations were smaller.

Animals↗

The corneal endothelium following autokeratoplasty. A case report.

An autokeratoplasty was performed on the left eye of a 64-year-old female, with the graft transferred from the contralateral, blind eye. The endothelial morphology and thickness of the central cornea were studied pre-operatively and yearly for 6 years after surgery. The endothelial cell density decreased rapidly during the first 2 years post-operatively (55.5%), after which cell loss occurred at a considerably slower rate (about 2% of the pre-operative cell density per year). During the observation period, the coefficient of variation in cell size stayed relatively constant (approximately 0.3). When the corneal thickness returned to normal 2 months after surgery, the endothelium showed a significant decrease in the percentage of hexagonal cells (15.0%). Between 2 months and 2 years post-operatively, the percentage of hexagonal cells gradually returned to normal. These endothelial changes noted are remarkably similar to those previously seen in homografts, suggesting that cell damage due to immunologic reactions may not be a major factor in long-term endothelial changes after homografting.

Cornea↗

Corneal endothelial changes associated with herpetic stromal keratitis.

Wide-field specular microscopy was performed on both eyes of 33 patients with unilateral herpetic stromal keratitis. Endothelial changes were quantitated by computerized morphometric analysis of individual cells. In the 16 patients with disciform keratitis, the corneal endothelium of the affected eyes showed no difference in cell density but demonstrated significant increases of variation in cell size (polymegathism) and shape (pleomorphism) when compared to the cells in the fellow unaffected eyes. The eyes with keratouveitis (17 patients), however, had marked polymegathism and pleomorphism of the endothelium and a distinctly lower endothelial cell density (mean, 19%) than the healthy fellow eyes.

Adolescent↗

Herpetic keratitis therapy to reduce recurrence.

Since the herpes simplex virus locates latently in the ganglia and is reactivated by certain triggers, the important problem in treatment is to prevent or reduce recurrence. The present study investigates the role of mechanical debridement in lessening the recurrence of dendritic keratitis in patients with herpetic epithelial keratitis. Group A was treated with mechanical debridement plus IDU, Group B with IDU alone. Also studied was the effect of steroid subconjunctival injection on herpetic recurrence in patients with herpetic stromal keratitis: Group C was treated with intravenous infusion of pepsin-treated gamma-globulin (PTGG) and steroid subconjunctival injection, Group D with steroid subconjunctival injection alone and Group E with intravenous infusion of PTGG alone. The recurrence rates of dendritic keratitis were 19% in Group A and 40% in Group B (average follow-up periods: 24 and 25 months). The recurrence rates of stromal keratitis were 61% in Group C, 64% in Group D, and 36% in Group E (average follow-up periods: 20, 19 and 15 months). The difference between Groups D and E was statistically significant (chi 2 test, P less than 0.05). The recurrence rates of dendritic keratitis were 18% in Group C, 21% in Group D and 7% in Group E. In conclusion, mechanical debridement tended to reduce the recurrence of herpetic epithelial keratitis and steroid subconjunctival injection to increase the recurrence of epithelial or stromal keratitis.

Administration, Topical↗

The effects of aldose reductase inhibitor on the corneal endothelial morphology in diabetic rats.

Diabetic rats were produced by intravenous injection of streptozotocin. Of these, eleven rats were treated with topical instillation of 0.5% aldose reductase inhibitor (ARI), while ten received vehicle alone. The corneal endothelium of these diabetic rats was examined by specular microscopy and compared to age-matched nondiabetic rats (ten rats). Computerized morphometric analysis of individual cells demonstrated that the endothelium of the untreated diabetic rats had marked polymegathism (increased coefficient of variation in cell area) and pleomorphism (decreased percentage of hexagonal cells), as previously observed in diabetic patients. Similar endothelial changes were also noted in the ARI-treated diabetic rats, but to a significantly lesser extent. These results suggest that topically applied ARI can be effective in reducing morphologic changes of the diabetic endothelium, and that activation of the sorbitol pathway may be implicated in the etiology of such endothelial changes.

Aldehyde Reductase↗

Induction of cytochrome P-450 in the rabbit eye by phenobarbital, as detected immunohistochemically.

The present study was aimed to demonstrate that cytochrome P-450 was induced by drug administration in particular tissues in the eye. Phenobarbital was used as an inducer. We showed immunohistochemically that cytochrome P-450 was induced in the cornea, conjunctiva and ciliary epithelium of rabbits after four days of intraperitoneal administration of phenobarbital at a dose of 80 mg per kg per day. We did not detect significant immunofluorescence in other ocular tissues. Prolonged administration caused degeneration of the ciliary epithelium, but not pathological change was seen in other ocular tissues. In this case, immunofluorescence was not detected in the ciliary epithelium but in the cornea, conjunctiva and lens.

Animals↗

Interferon enhances the natural killer cell activity of the retinoblastoma patients to autologous retinoblastoma cells.

The cytotoxic activities of the peripheral lymphocytes prepared from two retinoblastoma patients to freshly isolated autologous tumor cells were measured using 51Cr-release assay. The retinoblastoma cells of the two patients resisted lysis by unstimulated effectors, whereas interferon(IFN)-stimulated effector cells gave a significantly higher cytotoxicity. This result implies that IFN therapy may be potent in treating high-risk retinoblastoma patients.

Cytotoxicity, Immunologic↗