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Biomedical subjects

T Kuwabara

Publications and source records attributed to T Kuwabara.

At least 235 records · Page 13Linked to original sources

Effects of cyclosporine and other immunosuppressive drugs on experimental autoimmune uveoretinitis in rats.

Five immunosuppressive and anti-inflammatory agents were tested for their effects on development of experimental autoimmune uveoretinitis (EAU) and immune responses to S-antigen in rats immunized with this retinal antigen. When administered daily from day 0-14 after immunization, cyclosporine at 5-20 mg/Kg was nontoxic and yet effective in inhibiting the development of EAU for at least 30 days. All other tested drugs were found toxic at their immunosuppressive doses. Of these drugs, only cyclophosphamide (at 5-20 mg/Kg) was capable of inhibiting EAU in some of the treated rats for up to 30 days. Other agents, bredinin (40-100 mg/Kg), dexamethasone (0.2-0.4 mg/Kg), or colchicine (0.5 mg/Kg) produced only a delay in the disease onset. Cyclosporine was also unique in its effect on the immune responses of the rats by selectively inhibiting only the specific T-cell-mediated responses to S-antigen (delayed skin response and lymphocyte response in culture), while having no negative effect on antibody production or the lymphocyte response to the polyclonal mitogen, concanavalin A. Other drugs, when effective, inhibited all types of immune response. In addition, cyclosporine was capable of preventing EAU even when given to rats as late as from day 7 after immunization. Only cyclophosphamide (at 20 mg/Kg/day) had a similar effect on 1/3 of the rats, while other drugs only delayed or had no effect on the disease onset when given by this late schedule.

Animals↗

Adoptive transfer of experimental autoimmune uveoretinitis in rats. Immunopathogenic mechanisms and histologic features.

In order to learn about the immunopathogenic mechanisms of experimental autoimmune uveoretinitis (EAU), the capacity of lymphocytes to transfer the disease was studied. EAU was transferred to naive syngeneic rats by intraperitoneal injection of spleen or lymph node (LN) cells from S-antigen immunized rats, following their incubation in culture with either S-antigen or concanavalin A (Con A). In contrast, the same cells did not cause inflammatory changes in the recipient eyes when injected intravitreally. The identity of the lymphocytes that transfer EAU was determined by using monoclonal antibody enriched subsets of lymphocytes. EAU was transferred by the subset of helper/inducer T-cells, but not by T-cells of the suppressor/cytotoxic subset. Recipient rats of spleen or LN cells cultured with S-antigen exhibited both humoral and cellular immune responses to S-antigen. On the other hand, recipients of spleen cells cultured with Con A developed only cellular immune response to S-antigen. Yet, both groups of recipients fully developed EAU. The clinical and histologic changes in recipient rats closely resembled those in rats in which EAU was induced by active immunization. Severe tissue damage occurred at the photoreceptor cell layer, but inflammatory infiltration also was found in other ocular tissues. Involvement of polymorphonuclear leukocytes (PMNs) was noted throughout ocular tissues even in the eyes of recipients with no detectable antibodies to S-antigen, suggesting that the ocular PMNs infiltration in rats is not necessarily the result of an Arthus-like inflammatory process.

Animals↗

Long-term effects of Q-switched ruby laser on monkey anterior chamber angle.

In an attempt to clarify whether pulsed lasers might be able to cause permanent fistulas from the anterior chamber to the interior of the canal of Schlemm, slightly suprathreshold, low energy, small diameter Q-switched ruby laser pulses were applied to the trabecular meshwork of nine eyes of six rhesus monkeys. Clinical examinations during the next 2 months disclosed no adverse effect on the cornea, iris, lens, or retina. There was transient mild inflammation in five eyes. Intraocular pressure was not changed significantly; the facility determined by perfusion of the anterior chambers at 2 months was normal. Light microscopy and scanning electron microscopy show localized trabecular lesions; some are slightly indented, but there is no persistent penetration to Schlemm's canal. Endothelial cells, confluent with those of the cornea, cover the inner (anterior chamber) surface of the lesions. Cross-sections through the center of a lesion show that trabecular meshwork and Schlemm's canal have been obliterated by the treatment and healing; these changes are similar to those previously seen after argon laser monkey trabecular treatment. In the untreated areas, between pulsed laser application sites, trabecular meshwork and Schlemm's canal are normal by light microscopic and scanning electron microscopic examination. Any effect on IOP from this particular type of pulsed laser treatment of the trabecular meshwork is probably not due to trabeculopuncture and flow of fluid through the fistula.

Animals↗

31P-NMR studies on the energy metabolism of the living rat brain using a surface coil method.

We have examined the changes of the energetic metabolic state of rat and mouse brains under hypoxic hypoxia or ischemia using a 31P-NMR spectrometer with a surface coil. The NMR spectrometer has a super-conducting magnet providing a homogeneous magnetic field of 6.3 tesla. A probe was remodelled to accommodate an experimental animal in it. The animals were anesthetized with 1.0% or 1.5% halothane throughout the experiments. The optimal measurement conditions were a 90 degrees pulse width of 20 microsecond, and a 2 sec pulse repetition time. 200 acquisitions of FIDs was required for high spatially resolved signals. The Pcr/ATP ratio of the live, anesthetized rat brains was 1.76 +/- 0.46 (n = 8) for cerebra and 1.63 +/- 0.11 (n = 4) for cerebella. That of gerbil brains was 1.23 +/- 0.09 (n = 4). The Pcr/ATP ratio did not show any significant changes under both the conditions of hypoxic hypoxia or ischemia. The value of Pcr/Pi ratio decreased in the hypoxic conditions. The level of Pcr. of rat cerebrum decreased by 76.8 +/- 10.5% at 10% oxygen and by 57.3 +/- 15.7% at 5% oxygen compared with the value of 20% oxygen. The ATP level in the rat brain also decreased according to the degree of hypoxia. Cerebral ischemia was produced in the gerbil by ligation of the common carotid artery. The levels of Pcr. and ATP were severely depressed in the ischemic hemisphere but those of the intact side remained normal.

Adenosine Triphosphate↗

Gangliosidoses and the fetal retina.

Abnormal membranous cytoplasmic inclusions were found in the retinal ganglion cells of two fetuses with gangliosidosis. One was a documented case of incipient Tay-Sachs disease (Gm2) and the other a case of generalized gangliosidosis (Gm1). Both specimens were obtained iatrogenically in the 20th to 21st week of gestation after amniocentesis had indicated the enzyme deficiency.

Amniocentesis↗

CT findings in patients with gliomas, surviving more than 10 years.

After reviewing the latest CT scans of 23 mostly low grade glioma patients who survived more than 10 years after treatment, it was suggested that loss of the original tumour bulk and frequently the presence of porencephalic cavity replacing the original tumour, with a smooth lining which is not contrast-enhanced is essential to assume a clinical "cure" in the case of intrinsic cerebral gliomas. In the case of gliomas growing within the ventricle or subarachnoid space, tissue with calcium deposit but without contrast-enhancement was noted, although the number of cases was limited.

Adolescent↗

Comparison of retinal and cerebral vasculature in trypsin digest preparations.

The trypsin digestion technique for preparing flat mounts of the retinal capillary system was modified for comparable mounts of the cerebrocortical capillaries. These preparations, supplemented by electron microscopy, showed a basic similarity between the 2 systems, but the cortical capillaries have larger diameters, more abundant collateral channels, and less regularly spaced mural cells (intramural pericytes). The cortical capillaries did not show the right-angle branching of the precapillary arteriole characteristic of some retinal vessels, but they did show in the crotches of the branches an excess basement membrane that was not present in the retinal capillaries.

Capillaries↗

Localization of aldose reductase in the human eye.

The presence of the enzyme aldose reductase is increasingly being linked to diabetic complications. The distribution of this enzyme in human cornea, lens, retina, and optic nerve has been studied using specific antibodies against purified human placental aldose reductase raised in both rabbit and goat. The antisera from both animals gave equal, specific reactions. In frozen sections of ocular tissues, significant aldose reductase localization was reproducibly demonstrated in the endothelium and epithelium of the cornea and in the basal cell layers of the conjunctiva. In the lens, staining was observed in the epithelium and superficial lens fibers. In retinal sections, the presence of aldose reductase was demonstrated in the Mueller's cells, especially near the inner limiting membrane. It was also found in some ganglion and cone cells. In the optic nerve, positive staining was observed in the axon. All other cells of the tissues examined revealed only weak, nonspecific staining.

Adult↗

Purification of retinal S-antigen to homogeneity by the criterion of gel electrophoresis silver staining.

This report describes a procedure by which high performance liquid chromatographic (HPLC) techniques are used to obtain homogeneous S-antigen. Conventionally prepared S-antigen was purified further by fractionation on the anion exchange Mono-Q column followed by gel filtration on a TSK-3000 column. This procedure produced an S-antigen preparation, which appeared homogeneous by gel electrophoresis using the very sensitive silver staining method. The purified material retained its immunochemical and uveitogenic activity. The availability of homogeneous S-antigen will facilitate studies aimed at elucidating, at the molecular level, the mechanism by which S-antigen induces uveitis.

Animals↗

An association between susceptibility to experimental autoimmune uveitis and choroidal mast cell numbers.

An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.

Animals↗

Behavioral recovery in albino rats with glutamate-damaged retinas.

Adult, male, albino rats were trained to discriminate between two patterned stimuli in a T-maze. Performance on this task was assessed following intravitreal injection of 1 mumol glutamate. Discrimination performance declined to nearly random levels by 1 day postinjection and remained significantly depressed for 2 weeks. However, by 2 months after injection, there was evidence of behavioral recovery to preinjection levels despite significant loss of inner retinal neurons. Task-related experience immediately following or 2 months after injection proved both necessary and facilitative for recovery.

Animals↗