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Biomedical subjects

T Kuwabara

Publications and source records attributed to T Kuwabara.

At least 163 records · Page 9Linked to original sources
PubMed1989

Cryopexy enhances experimental autoimmune uveoretinitis (EAU) in rats.

Treatment of rat eyes with cryopexy enhanced the development of experimental autoimmune uveitis (EAU) in these eyes. The enhancement of EAU by cryopexy was particularly pronounced when the disease was induced by active immunization in rats of a low responder strain (Wistar Furth), or by adoptive transfer with lymphocytes sensitized against S-antigen. The disease enhancement was expressed by earlier onset of clinical symptoms and by more severe inflammatory changes. Histological examination of cryopexy-treated eyes showed focal necrosis and inflammation, confined to the affected sites. Immunohistochemical analysis of the inflammatory infiltration revealed it consists mainly of macrophages and T-lymphocytes of the helper and suppressor subsets. In addition, increased expression of class II antigens was observed in affected areas, on both inflammatory and resident ocular cells. Using electron microscopy and Evans blue angiography we could show breakdown of the blood-retinal barrier at the treated sites. Histological examination of eyes with EAU following cryopexy showed localization of the early inflammation at the injured site. The data are interpreted to suggest that the enhanced EAU in cryopexy-treated eyes is mainly due to the breakdown of the blood-retinal barrier, the accumulation of lymphoid cells and the increased expression of class II antigens, which facilitates antigen presentation.

Animals↗
PubMed1989

[Successful treatment of secondary erythroleukemia with androgen].

A case of secondary erythroleukemia treated with apparent success with androgen is reported. The patient is 63-year-old Japanese female. She had a history of multiple myeloma and had been treated with melphalan, vincristine and prednisolone. She developed erythroleukemia 88 months after the initiation of chemotherapy, while her myeloma was a complete remission. She was treated first with vitamin D3 with no beneficial effect and subsequently with 0.5 mg/kg of mepitiostane. A hematologic improvement began two months from the initiation of androgen therapy, and a complete remission of erythroleukemia was attained thereafter. A chromosomal abnormality of bone marrow cells, which was observed at the time of developing erythroleukemia, also disappeared after the treatment. She remained in good condition and hematologic remission under the androgen therapy at the latest follow-up, 1-year after the development of erythroleukemia. Androgen therapy may be considered as a useful treatment for secondary erythroleukemia.

Androstanols↗
PubMed1989

[The observation of blood-brain barrier of organic mercury poisoned rat: a Gd-DTPA enhanced magnetic resonance study].

Permeability of the blood-brain barrier (BBB) of methylmercury chloride (MMC) intoxicated rat brain was studied in vivo by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). MMC intoxicated rat brain showed the prolonged T1 in the cerebral white matter and prolonged T2 in the cerebellar cortex. After Gd-DTPA administration, T1 of cerebral and cerebellar white matter shortened from 1.647 to 1.344 sec., and 1.290 to 1.223 sec. respectively. On the contrary, T2 showed no change after Gd-DTPA injection. It was concluded that, although the shortening of T1 after Gd-DTPA enhancement was rather little when compared with experimental brain ischemia, the shortening of the relaxation time of the MMC intoxicated rat brain was caused by the increased permeability of BBB.

Animals↗
PubMed1988

NIH conference. Cystinosis: progress in a prototypic disease.

OBJECTIVE: To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis. DESIGN: Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy. SETTING: University centers in the United States and Canada. PATIENTS: One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration. INTERVENTION: Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight.d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications. MEASUREMENTS AND MAIN RESULTS: Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [+/- SE], 0.64 +/- 0.04 mL/s.1.73 m2 [38.5 +/- 2.5 mL/min.1.73 m2] in the cysteamine group compared with 0.50 +/- 0.03 mL/s.1.73 m2 [29.7 +/- 2.0 mL/min.1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old. CONCLUSIONS: Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine.

Adolescent↗
PubMed1988

Suramin keratopathy.

Vortex keratopathy occurred in six patients given high-dose intravenous suramin for adrenocortical carcinoma. The corneal findings were bilateral and symmetric. Two patients complained of foreign-body sensation. One patient developed opacities of the anterior lens epithelium. Histopathologic studies of the eyes in one patient showed intraepithelial apical deposits in the cornea, conjunctiva, and lens epithelia. By electron microscopy, these deposits were found to be membranous lamellar inclusion bodies. These findings, as demonstrated by osmium-PAS staining and electron microscopy, were similar to those in other drug-induced lipid storage diseases.

Adrenal Cortex↗
PubMed1988

Immunopathologic study of Vogt-Koyanagi-Harada syndrome.

We studied an enucleated eye from a patient with a 30-year history of Vogt-Koyanagi-Harada syndrome using both conventional and immunohistochemical techniques. Clinically, the eye was in the end stage of Vogt-Koyanagi-Harada syndrome, and was characterized by the absence of inflammation, large areas of chorioretinal scarring, and pigmentary changes. Histopathologic examination showed marked retinal gliosis, extensive chorioretinal adhesion and scar formation, migration of pigment into the retina, and severe retinal pigment epithelial changes. However, foci of mild to moderate nongranulomatous inflammation of the uvea were observed. These foci contained infiltrating cells that were mainly T lymphocytes with B lymphocyte aggregates at the center. Scattered macrophages were also noted in the uvea and retina. These findings suggest that both the cell-mediated and humoral immune arms may play roles in the pathogenesis of Vogt-Koyanagi-Harada syndrome.

Aged↗
PubMed1988

Characterization of a suppressor cell line which downgrades experimental autoimmune uveoretinitis in the rat.

A Ts lymphocyte line was isolated from spleens of rats primed with the retinal soluble Ag (SAg) in the anterior chamber of the eye. This line could inhibit in vitro SAg-driven proliferation of uveitogenic Th lymphocytes, in a radioresistant, Ag-independent manner. Adoptively transferred Ts line cells were found to downgrade experimental autoimmune uveoretinitis in actively immunized syngeneic recipients. The initial surface phenotype (OX8+) of the Ts line was unstable in vitro, however, the cells expressed suppressor function irrespective of phenotype. The mechanism of suppression did not appear to involve consumption of IL-2 or direct cytolysis of uveitogenic Th lymphocytes, but rather the production of a soluble suppressor factor. These findings may suggest an in vivo role for suppressor lymphocytes, capable of inhibiting primed Th cells, in the regulation of experimental autoimmune uveoretinitis.

Animals↗
PubMed1988

Intraocular trafficking of lymphocytes in locally induced experimental autoimmune uveoretinitis (EAU).

Experimental autoimmune uveoretinitis (EAU) was induced in naive Lewis rats by intravitreal adoptive transfer of 10(6) long-term S-antigen (S-Ag)-specific syngeneic T-lymphocyte lines of helper/inducer phenotype (ThS). These cells were stimulated with the T-cell mitogen concanavalin A (Con A) in culture for 48 hr and subsequently labeled with tritiated thymidine. Lymph node cells (LNC) cultured in parallel were used as controls. Histopathology and light microscopic autoradiography of the ocular tissue was performed at several time points to analyze the cell migration in relation to the development of EAU. The disappearance of both types of lymphocytes from the vitreous was similar and large numbers of host leukocytes were attracted into the vitreous. However, significantly more S-Ag-specific cells penetrated the retina and induced EAU (P less than 0.008). These results suggest that the development of EAU by intravitreal injection of S-Ag-specific T lymphocytes occurs by the migration of antigen-specific cells into the retina and recognition of the specific antigen, with subsequent release of soluble mediators that interact with the host effector cells, ultimately leading to specific photoreceptor damage.

Animals↗
PubMed1988

A simple and efficient procedure for the isolation of high-quality phage lambda DNA using a DEAE-cellulose column.

A simple and rapid procedure for purifying large quantities of bacteriophage lambda particles and DNA is described. The procedure involves DEAE-cellulose column chromatography of the phage particles and elution of the phage particles from the column with a low-ionic-strength buffer. The resulting phage were well separated from RNA, DNA, and proteins derived from Escherichia coli host cells. The lambda DNA was prepared from the purified phage particles by the conventional method of phenol extraction and ethanol precipitation. This procedure did not use nucleases, proteases, detergents, or CsCl density gradient centrifugation. The lambda DNA obtained by this method was equivalent in purity to the material prepared by CsCl density gradient centrifugation and amenable to restriction enzyme digestion, ligation, radiolabeling, and double-stranded DNA sequencing. A detailed protocol is described for obtaining 0.5 to 1.0 mg DNA from a 1-liter liquid lysate in less than 5 h. This procedure is simple, inexpensive, and timesaving, and is particularly suitable for large-scale isolation of lambda DNA.

Bacteriophage lambda↗
PubMed1988

Effects of continuous light exposure on the rat retina and pineal gland.

We examined the effects of intense continuous light (400 ftc for 10 days) on the morphology and immunoreactivity of the rat retina and pineal gland. The light treatment caused severe degeneration in the retina, with loss of most photoreceptor cells, and produced a marked decrease in S-antigen immunoreactivity in this organ. Unlike the retina, the light treatment had minimal effects on the histological structure of the pineal gland. However, pineal glands of light-treated rats exhibited a substantial reduction in their S-antigen immunoactivity, as demonstrated immunohistochemically and quantitatively verified by the rocket immunoelectrophoresis technique: pineal glands of light exposed rats had approximately two-thirds of the S-antigen immunoactivity of the untreated controls. Light treatment was also found to reduce both uveoretinitis and pinealitis in rats immunized with S-antigen. Yet pinealitis was not affected by light exposure in rats, as they were enucleated before treatment. This study thus provides new information to support the notion that the mammalian pineal gland is directly associated with light detection by the retina.

Animals↗
PubMed1988

Range of toxicity of topical cysteamine in rabbit eyes.

Cysteamine eye drops in concentrations from 0.1% to 10% were tested in albino rabbits in both short and long-term experiments. Toxicity, consisting of an inflammatory response, was proportional to the cysteamine concentration and absent at concentrations at or below 0.5%.

Animals↗
PubMed1988

Traumatic intraventricular hemorrhage: report of twenty-six cases and consideration of the pathogenic mechanism.

A series of 26 patients suffering traumatic intraventricular hemorrhage (IVH) after closed head injury is reviewed, and the pathogenic mechanism of the traumatic IVH is discussed considering the site of origin of the IVH. Computed tomographic detection of the origin of the IVH was possible in 15 patients (Group 1): 6 had frontal or temporal contusional intracerebral hemorrhage spreading into the ventricle (Subgroup A), 5 had the original hemorrhage in the caudate nucleus (Subgroup B), and 4 originally bled in the thalamus (Subgroup C). The origin of the IVH was not determined in 11 patients (Group 2): 6 had concomitant hemorrhage around the brain stem (Subgroup D), and 5 had small IVH with or without small intracerebral hemorrhage (Subgroup E). The site of impact was not uniform in Subgroup A, whereas the other four subgroups usually had frontal or occipital impact. In Subgroup A, the IVH was discovered more than several hours after trauma. In the other four subgroups, however, the IVH was detected in as short a time as 0.5 to 1.5 hours after trauma. In Subgroups B and C, the impact along the long axis of the skull and the early occurrence of hemorrhage in the basal ganglia suggest that shear injury between the perforating vessels and the basal ganglia may be the responsible mechanism. The several other possible mechanisms in Subgroups D and E are reviewed and discussed in relation to diffuse brain injury.

Adolescent↗
PubMed1988

Cyanogen bromide fragments of bovine interphotoreceptor retinoid-binding protein induce experimental autoimmune uveoretinitis in Lewis rats.

Interphotoreceptor retinoid-binding protein (IRBP), a retinal specific antigen, induces experimental autoimmune uveoretinitis (EAU) when injected into Lewis rats. Here we report that certain cyanogen bromide fragments of IRBP are capable of inducing EAU. Bovine IRBP, reduced and S-carboxymethylated, was subjected to cyanogen bromide cleavage. This CNBr digest was subjected to reversed-phase high performance liquid chromatography. Three fragments were purified to apparent homogeneity. These three fragments were subjected to gas-phase amino-terminal sequencing analysis. All three yielded single sequences, confirming their purity. On the basis of this amino-terminal sequencing and sequencing of cDNAs encoding bovine IRBP, two of these sequences, named CB-58 and CB-71, were localized to the C-terminal one-third of the IRBP molecule, whereas the third, a subfragment thought to result from cleavage at a tryptophan residue and named CB-47, was localized to the N-terminal one third of the protein. CB-71 and CB-47 shared a strong homology, suggesting a putative internal gene duplication event in the evolution of IRBP. All three of these fragments when injected into Lewis rats caused moderately severe EAU with early onset at relatively low doses. The histopathologic changes induced were indistinguishable from those caused by the intact protein. It would seem, therefore, that bovine IRBP contains multiple uveitogenic sites.

Amino Acid Sequence↗
PubMed1988

Synthetic peptides derived from IRBP induce EAU and EAP in Lewis rats.

In an earlier study we isolated three cyanogen bromide cleavage fragments of bovine IRBP that exhibited high levels of immunopathogenicity, producing inflammatory changes in the eyes (EAU) and pineal gland (EAP) of Lewis rats. These fragments have been localized within the IRBP sequence. In order to identify these putative immunopathogenic epitopes of IRBP, nine selected peptide sequences were synthesized and tested for the induction of disease in Lewis rats. Seven of the peptides were found inactive in producing disease while two closely related peptides, designated R4 (23-mer) and R9 (27-mer) were found to reproducibly induce EAU and EAP in immunized rats. No good correlation was found between the immunopathogenicity of the nine tested peptides and their amphipathicity: peptides R4 and R9 were not predicted to form strong amphipathic helices, while peptides selected for their high predicted helical amphipathicity were not immunopathogenic. EAU induced by peptides R4 and R9 was less severe and had a longer onset time than the disease induced by whole IRBP. In addition, the inflammatory changes induced by R4 and R9 in the posterior segment of the eye were less acute than those induced by whole IRBP and included granuloma formation and perivasculitis, features which are not generally seen in rats immunized with whole IRBP. Thus, the changes induced by R4 and R9 more closely resemble those which are characteristically found in human eyes affected by certain uveitic diseases than do changes produced by the intact protein.

Amino Acid Sequence↗
PubMed1988

Subdural tension pneumocephalus following surgery for chronic subdural hematoma.

The computerized tomography (CT) findings were analyzed in five cases of subdural tension pneumocephalus following surgery for chronic subdural hematoma. They were compared with CT scans in 14 cases of asymptomatic subdural pneumocephalus. In this study, two new CT findings were identified that suggest increased tension of the subdural air. Subdural air separates and compresses the frontal lobes, creating a widened interhemispheric space between the tips of the frontal lobes that mimics the silhouette of Mt. Fuji. The presence of air between the frontal tips associated with massive air inclusion over the frontal lobes presumably indicates increased tension of the subdural air. The "Mt. Fuji sign" was seen in four of the five cases with subdural tension pneumocephalus. The other finding was the presence of multiple small air bubbles scattered through several cisterns ("air bubble sign"). It is postulated that these air bubbles enter the subarachnoid space through a tear in the arachnoid membrane caused by increased tension of air in the subdural space. This finding was seen in four cases with subdural tension pneumocephalus. These two CT findings are helpful in making a diagnosis of subdural tension pneumocephalus following surgery for chronic subdural hematoma.

Aged↗