Biomedical subjects

T Tokoro

Publications and source records attributed to T Tokoro.

At least 55 records · Page 3Linked to original sources

PubMed1998

Zinn-Haller arterial ring observed by ICG angiography in high myopia.

AIMS: To delineate the entire Zinn-Haller arterial ring angiographically in vivo. METHODS: 382 highly myopic eyes (210 patients) with refractive errors greater than -8.25 D were examined using indocyanine green (ICG) videoangiography. A control group of 80 eyes (40 patients) had refractive errors within plano +/- 3D. RESULTS: The Zinn-Haller ring was visible in 206 of 382 highly myopic eyes (53.9%) by ICG angiography. Although only a part of the Zinn-Haller ring was visible in 162 of 206 eyes, in the remaining 44 eyes it was observed almost completely around the optic nerve head. No anastomotic channels between lateral and medial short posterior ciliary arteries were filled by ICG angiography. In 22 of the 44 eyes (50.0%) the Zinn-Haller ring was supplied by branches of the lateral and medial short posterior ciliary arteries; in seven eyes, it was supplied only by the lateral short posterior ciliary artery; and in seven eyes, it was supplied only by the medial short posterior ciliary artery. In none of the control subjects was the Zinn-Haller ring visible by ICG angiography. CONCLUSIONS: The Zinn-Haller ring observed by ICG angiography was not a complete collateral circle between lateral and medial posterior ciliary arteries. Also, the patterns in supply vessels to the Zinn-Haller ring varied. ICG angiography made possible the detailed observation of the Zinn-Haller ring in human eyes in vivo.

Adolescent↗

PubMed1998

Clinical course of newly developed or progressive patchy chorioretinal atrophy in pathological myopia.

Regional chorioretinal atrophy in the posterior fundus (patchy chorioretinal atrophy) in pathological myopia impairs vision severely when it covers the macula. The aim of this study was to assess the course of development and progression of patchy chorioretinal atrophy in pathological myopia. The location and progression of patchy chorioretinal atrophy that was either newly developed or had progressed during the follow-up period (mean 5.25 years) were analyzed. A total of 41 lesions of patchy atrophy were newly developed in 30 eyes of 25 patients. These lesions were more likely to occur in marginal regions of a posterior staphyloma but frequency per unit area was highest in the macula. There were 138 lesions of patchy chorioretinal atrophy that progressed in 75 eyes of 53 patients. Sixty percent of the lesions of patchy chorioretinal atrophy in marginal regions of a posterior staphyloma spread toward the center. Seventy percent of the lesions of patchy chorioretinal atrophy in the macula spread in all directions. Fluorescein angiography of newly developed patchy chorioretinal atrophy showed hyperfluorescence in 50% and hypofluorescence in 27%. Fluorescein angiography of progressive lesions of patchy chorioretinal atrophy showed hypofluorescence in 69%. Fluorescein angiography of some progressive areas of patchy chorioretinal atrophy, which showed a change from hyperfluorescence to hypofluorescence within several years, suggested that damage to the retinal pigment epithelium preceded the progression of the patchy chorioretinal atrophy. In conclusion, the patchy chorioretinal atrophy is most likely to occur in the macula and to enlarge in all directions. And it is suggested that the patchy chorioretinal atrophy which shows hyperfluorescence by fluorescein angiography should be kept under observation because our data suggest that this finding indicates progression in the future.

Adult↗

PubMed1998

Retinoic acid increases in the retina of the chick with form deprivation myopia.

We previously reported that expression of retinoic acid receptor beta increases in the sclera of the 2-week-old chick with form deprivation myopia (FDM) and that all-trans-retinoic acid (t-RA) influences proliferation and differentiation of scleral cells. The purpose of this study was to quantify t-RA in the retina of the chick with FDM and to investigate the role of t-RA in FDM in the chick. FDM was induced in 2-day-old chicks by placement of a translucent plastic goggle over one eye, with the contralateral eye used as a control. After 5 days, the chicks were sacrificed. t-RA was extracted from neural retina and served for high-performance liquid chromatography analysis. 3H-t-RA was used for normalization. Pieces of the retinae from 5 eyes served as one sample. As a result, t-RA was 09.60 +/- 0.86 ng/eye (0.387 +/- 0.056 ng/mg protein) in the myopic retina was significantly higher than that in the control (p < 0.05, n = 7). These results demonstrate that t-RA increases in the retina within 5 days after visual deprivation. This finding suggests that t-RA may play a role in the metabolic changes in FDM.

Animals↗

PubMed1998

Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a metastatic bone tumor.

Some occult thyroid carcinomas are hypothesized to regress and be eventually obliterated. We report here a patient whose condition supports this hypothesis. A 51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion. Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100 microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml). The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor, whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed papillary proliferation of large atypical cells, which were immunohistochemically positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma was therefore strongly suspected. He underwent a total thyroidectomy and the thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened atrophied follicles, but no carcinomatous foci were found. He was treated with I-131 and scintigraphy after the ingestion showed distinct accumulation in the rib tumors similar to that before thyroidectomy. No other abnormal uptake was observed. It is suggested that the primary occult thyroid papillary carcinoma regressed and was obliterated possibly by some immunologic or other host-resistance factors after it metastasized to the distant bone.

Bone Neoplasms↗

PubMed1998

Variant angina in isolated adrenocorticotropin deficiency, inappropriate vasopressin secretion and Hashimoto's thyroiditis.

We report a 62-year-old male patient who had variant angina and isolated adrenocorticotropic hormone (ACTH) deficiency. His serum sodium concentration was low and vasopressin was inappropriately high for the low plasma osmolality. Serum free thyroxine (FT4) was low and thyroid stimulating hormone (TSH) was high with positive anti-thyroperoxidase antibodies, compatible with Hashimoto's thyroiditis. Treatment with Amrodipine and hydrocortisone relieved chest symptoms and hyponatremia, and hypothyroidism was also normalized. It is suggested that coronary artery spasm may be related to cortisol deficiency and/or inappropriately high vasopressin secretion and that hypothyroidism was ameliorated because the reduced responsiveness to TSH returned to normal due to hydrocortisone supplement.

Adrenocorticotropic Hormone↗

PubMed1998

[Developmental mechanism of low myopia and therapeutic possibilities. A review].

We studied the developmental mechanism of low myopia and the possibility of its drug treatment. I. Prevalence of myopia. According to surveys by the Japanese Ministry of Education, Science, Sports and Culture, the frequency of myopia in school children has gradually increased. We examined office workers from 20 to 60 years of age over a 3-year period. Myopia progression was observed in the thirties and fourties. Late-onset myopia is an important problem around the world. II. Developmental mechanism of low myopia. 1. Reduction of refraction after cycloplegia was statistically significant in adults after their twenties. We measured accommodative hysteresis after a close visual task. Accommodative hysteresis persisted for a long time in late-onset and adult-onset myopia. Continuous ciliary contraction seems to be related to late-onset myopia. 2. Bovine ciliary muscle strips were suspended in a Magnus double tube. The changes in isometric tension of the strips, when chemicals were added, were measured with a force-displacement transducer. After the addition of the cholinergic agonist carbachol, the strips of ciliary muscle produced a tonic contraction. When the muscarinic receptor antagonist cyclopentolate was added, relaxation was produced. After the addition of ET-1, a dual response occurred which consisted of a moderate relaxation and a long-lasting contraction. The mean contraction caused by ET-1 was weak but continuous compared to carbachol. The contractile response was inhibited by an ETA receptor antagonist. Also, when takusha, one component of gorei-san, a Chinese drug, was added to the ciliary muscle strips, contraction with ET-1 was attenuated. Contraction of the ciliary muscle with ET-1 was attenuated after addition of sodium nitroprusside (SNP), an NO donor. This reaction suggests that NO causes relaxation of the bovine ciliary muscle through the activation of guanylyl cyclase and an increase in cyclic GMP. Currently, at least 5 muscarinic receptor subtypes are recognized; they are named M1 to M5. The effects of M1, M2, and M3 on the contractile response to transmural electrical stimulation of the bovine ciliary muscle were studied. The contractions produced by transmural electrical stimulation were greatly attenuated by 4-DAMP as an M3 antagonist. 3. We measured autofluorescence of the lens by fluorophotometry. A statistically significant relation was found between autofluorescence of the lens and refraction. 4. Possibility of axial elongation: The anterior and posterior suprachoroidal spaces are different anatomically and physiologically. When the choroid is stretched forward by accommodation, the intraocular pressure may exert more influence on the posterior part of the sclera, than on the anterior part. Using a fluorophotometer, fluorescence leakage at a site 3 mm in front of the retina was examined. Intensity of fluorescence 3 mm in front of the retina was strong in late-onset myopia. This may indicate disturbance of the barrier of the retinal pigment epithelium. When cultured fibroblasts of the sclera of the chick embryo was stretched by a stretching apparatus, proliferation of the cultured cells was inhibited. Therefore, some influence may involve the posterior part of the eyeball. III. Possibility of drug treatment of low myopia: From these results, muscarinic receptor antagonists (especially M3), ET receptor agtagonists, and NO donors are possible drugs for low myopia treatment. As there are many causative factors of low myopia, there are several treatment methods to be evaluated.

Adolescent↗

PubMed1998

A family with Leber's hereditary optic neuropathy with mitochondrial DNA heteroplasmy related to disease expression.

A Japanese family has members with Leber's hereditary optic neuropathy resulting from the heteroplasmic 11778 mutation and the homoplasmic 4216 mutation. Quantitative determination of heteroplasmy was performed by a combination of polymerase chain reaction and single-strand conformation polymorphism analysis. The association between heteroplasmy and clinical features was determined. Eleven people from the maternal side of the family, including four affected and seven unaffected members, showed heteroplasmy of the mtDNA mutation ranging from 5% to more than 95%. Four possibly affected patients had more than 90% of the mutant mtDNA. Seven unaffected people had mutant mtDNA ranging from 5% to 77%. A recovery episode of visual acuity was noted in the history of three of the four patients. Heteroplasmy is likely to be a factor in the expression of disease in this family.

Adult↗

PubMed1997

Apomorphine inhibits the growth-stimulating effect of retinal pigment epithelium on scleral cells in vitro.

Visual deprivation of the chicken eye causes axial elongation with high myopia. The cartilaginous layer of the myopic sclera shows an increase of mitotic activity. Previous studies reported that the in vivo administration of apomorphine, a dopamine nonselective agonist, effectively prevents visual-deprivation myopia. Because the retinal pigment epithelium (RPE) regulates growth of the sclera as we and others have shown previously, it is speculated that the RPE cells may play an important role in this preventive effect of apomorphine. In this study, to clarify the mechanism by which the administration of apomorphine inhibits the proliferation of scleral chondrocytes in vivo, we have investigated the effect of apomorphine on the proliferation of scleral chondrocytes with or without co-cultured RPE cells in vitro. We previously demonstrated that cell proliferation of scleral chondrocytes remarkably increases with co-cultured RPE cells. In this study, we found that apomorphine at concentrations of higher than 2 x 10(-5) M dramatically reduced the growth-stimulatory effect of RPE cells on the scleral chondrocytes, whereas the inhibitory effect of apomorphine on the proliferation of scleral chondrocytes without RPE cells was very little. Our results strongly suggest that apomorphine may reduce the production and/or release of some humoral factors from RPE cells, which stimulate the growth of scleral cells. There is also a possibility that apomorphine reduces the reactivity of scleral cells to the humoral factors released from RPE cells.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1997

Regional scleral changes in form-deprivation myopia in chicks.

Similar neurochemical events appear to be involved in the development of myopia in chicks and mammals. The rapid post-hatching development of the chick is ideal for studying experimental myopia. In this investigation, one eye of 2-day-old chicks was deprived of form vision for 2 weeks and then compared to the fellow, non-deprived eye by immunohistochemistry and light and electron microscopy. All deprived eyes showed a high refractive error and ocular enlargement. In deprived eyes, the posterior cartilaginous sclera was thicker and the fibrous sclera of the same section was thinner than the control. Scleral morphological changes were restricted to a central button 6-7 mm in diameter (the posterior pole) within the posterior hemisphere, further divided into posterotemporal and posteronasal parts. The most enlarged, posterior cartilaginous structure of deprived sclera could be divided into an inner and an outer zone. The inner zone had many unevenly-arranged chondrocytes, each having a well-developed granular endoplasmic reticulum and Golgi complex and a very irregular cell surface. Numerous S-phase cells and isogenous groups were detected in the outer zone. Hypertrophic chondrocytes were often observed in the innermost region of the outer zone and the outermost region of the inner zone. The boundary between the outer fibrous sclera and the cartilaginous sclera was irregular and obscured in myopic eyes. Spindle-shaped chondrocytes were seen to be in contact with each other. Thick collagen fibrils, usually seen only in the outer fibrous sclera, were present among the chondrocytes. Results of this morphological study suggest an increased proliferation of chondrocytes and active synthesis of extracellular matrix in visually deprived eyes. The elongation of the ocular axis that accompanies myopia is caused primarily by an active remodeling and differentiation in a restricted section of the posterior scleral cartilage. These facts indicate the posterior scleral cartilage may be more immature than cartilage in anterior and lateral segments.

Animals↗

PubMed1997

A possible role of endogenous inhibitor for nitric oxide synthesis in the bovine ciliary muscle.

The present experiments were designed to investigate the possible role of endogenous methylarginine derivatives such as NG-monomethyl-L-arginine, asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine for the nitric oxide synthesis in the bovine ciliary muscle. The contents of asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine in the bovine ciliary muscle were determined to be 370.2 +/- 27.6 (n = 5) and 182.4 +/- 22.9 (n = 5) pmoles g-1 wet weight, respectively by means of the automated high-performance liquid chromatography. NG-Monomethyl-L-arginine was below the assay limits. On the basis of the total tissue water content (0.792 +/- 0.006 ml g-1 wet weight, n = 14), the concentrations of asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine were tentatively estimated to be (4.7 +/- 0.3) x 10(-7) M (n = 5) and (2.3 +/- 0.3) x 10(-7) M (n = 5), respectively. A23187 (10(-7)-3 x 10(-4) M) produced a concentration-dependent relaxation of the ciliary muscle strips which had been contracted with 10(-5) M carbachol. Authentic asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-6)-3 x 10(-4) M), but not symmetrical NG,N'G-dimethyl-L-arginine (3 x 10(-4) M), inhibited the 10(-6) M A23187-induced relaxation in a concentration-dependent manner. The inhibition with asymmetrical NG,NG-dimethyl-L-arginine (10(-4) M) was reversed by an addition of 3 x 10(-3) M L-arginine, but not by 3 x 10(-3) M D-arginine. The A23187 (10(-6) M)-induced relaxation was enhanced by 3 x 10(-3) M L-arginine or superoxide dismutase (50 U ml-1), whereas it was inhibited by carboxy-PTIO (3 x 10(-4) M), a scavenger of nitric oxide, or methylene blue (10(-5) M), an inhibitor of guanylate cyclase. The carbachol-induced contraction was enhanced by asymmetrical, NG,NG-dimethyl-L-arginine (10(-5) M) and inhibited by 3 x 10(-3) M L-arginine. Any effect of prostanoid formation during the A23187-induced relaxation was ruled out by using indomethacin (10(-5) M). Sodium nitroprusside (10(-5) M), a donor of nitric oxide, also produced a relaxation, which was inhibited by methylene blue (10(-5) M) or carboxy-PTIO (3 x 10(-4) M) and was augmented by superoxide dismutase (50 U ml-1), but unaffected by asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-4) M) or L-arginine (3 x 10(-3) M). These results lead us to speculate that the nitric oxide synthesized endogenously from L-arginine may play a role for mediating relaxation of the bovine ciliary muscle and that the endogenous asymmetrical NG,NG-dimethyl-L-arginine may be involved in inhibiting the biosynthesis of nitric oxide when there are increased intracellular concentrations of the methylarginine under certain circumstances.

Animals↗

PubMed1997

Indocyanine green angiography of retrobulbar vascular structures in severe myopia.

PURPOSE: To evaluate angiographic findings of retrobulbar arteries and veins in severely myopic patients. METHODS: We examined 416 severely myopic eyes (213 patients) with refractive errors greater than -8.25 diopters using indocyanine green videoangiography. A control group of 74 eyes (37 patients) had refractive errors within plano +/- 3 diopters. Four severely myopic patients underwent computed tomographic angiography to identify the entire intraorbital course of retrobulbar veins. RESULTS: Of 416 severely myopic eyes, 231 (55.5%) exhibited retrobulbar arteries, which were tortuous and pulsatile behind the posterior pole of the globe. Retrobulbar arteries connected directly with choroidal arteries temporal to the macular area. In 17 of these 231 eyes, retrobulbar arteries were also observed nasal to the optic nerve head, continuous with the Zinn-Haller ring around the optic nerve head and directly connected with choroidal arteries. In 39 severely myopic eyes (31 patients), indocyanine green angiography disclosed retrobulbar veins, most of which coursed vertically just behind the posterior pole of the globe. These retrobulbar veins originated as an inferior vascular network of the inferior orbital vein and drained into the superior orbital vein in the upper orbit. CONCLUSION: Retrobulbar arteries observed in this study were temporal and nasal short posterior ciliary arteries. Only the lateral collateral vein, which was one of the collateral channels between the superior and inferior orbital veins, was visible in severely myopic eyes. Indocyanine green angiography is useful in evaluating retrobulbar vascular structure in severely myopic eyes.

Adolescent↗

PubMed1997

The efficacy of cooling on excimer laser photorefractive keratectomy in the rabbit eye.

We cooled the surface of the cornea to reduce the thermal damage by the excimer laser ablation and referred to this method as "cooling photorefractive keratectomy" (cooling PRK). We performed conventional PRK and cooling PRK on rabbits' eyes and measured the thermal change during laser ablation. We also examined the degree of subepithelial haze and the tissues with a light microscope and an electron microscope. Normal corneal temperature of live rabbit corneas was about 32 degrees C and it rose to 41 degrees C after 300 laser shots. However, when we cooled the rabbit corneas to 24 degrees C with continuous irrigation of chilled BSS PLUS solution before laser ablation, the temperature rose only to 34 degrees C after the same ablation. Slit-lamp evaluation showed that more severe corneal haze occurred with the conventional PRK procedure. At 2 weeks postoperatively, the mean haze score was 1.77 +/- 0.87 in the conventional PRK and 0.87 +/- 0.38 in the cooling PRK (P < 0.01). Light-microscopy examination showed epithelial hyperplasia and fibroblasts, type III collagen, and heat shock protein-70 in the subepithelium of corneas with conventional PRK procedure than with cooling PRK. Under the electron microscope, more disruption of the layers of fibroblasts and collagen fibrils was observed in the conventional PRK procedure than that of the cooling PRK. In conclusion, the cooling of the corneal surface in PRK effectively reduces tissue damage related to subepithelial haze and may enable us to reduce the degree of myopic regression.

Animals↗

PubMed1997

Nitric oxide-induced ciliary muscle relaxation during contraction with endothelin-1 is mediated through elevation of cyclic GMP.

PURPOSE: Nitric oxide (NO) relaxes ciliary smooth muscle, and endothelin-1 (ET-1) is reported to regulate ciliary muscle tone. Despite the physiological significance of nitric oxide and ET-1, very few studies have attempted to characterize the mutual modes of action of these mediators in this tissue. Thus, the present experiments were designed to investigate a possible relaxation mechanism of nitric oxide in bovine ciliary muscle that has been contracted by ET-1. METHODS: The effects of sodium nitroprusside (SNP), as a nitric oxide donor, methylene blue, as an inhibitor of guanylate cyclase, and 8-bromo-cyclic GMP on the bovine ciliary muscle contracted with ET-1 were examined. The changes in cyclic GMP level and relaxation, in response to SNP alone or in combination with 3-isobutyl-1-methylxanthine (IBMX) as a nonselective inhibitor of phosphodiesterases, were also determined. RESULTS: Sodium nitroprusside (SNP) produced a concentration-dependent relaxation, which was significantly (p < 0.005) augmented by 10(-5) M 3-isobutyl-1-methylxanthine (IBMX) and significantly (p < 0.005) attenuated by 3 x 10(-5) M methylene blue as an inhibitor of guanylate cyclase. The relaxation in response to SNP was accompanied by an increase in the cyclic 3':5' guanosine monophosphate (cyclic GMP) level, which was again significantly (p < 0.05) augmented by 10(-5) M IBMX and significantly (p < 0.005) attenuated by 3 x 10(-5) M methylene blue. The exogenously applied 8-bromo-cyclic GMP relaxed the ciliary muscle strips during the contraction caused by ET-1. CONCLUSIONS: These results lead us to assume that NO generated from SNP is closely related to cyclic GMP production via the activation of guanylate cyclase and, in turn, causes a relaxation response in the bovine ciliary muscle contracted with ET-1.

1-Methyl-3-isobutylxanthine↗

PubMed1997

The long-term follow-up of a highly myopic patient with a macular vortex vein.

We followed a highly myopic patient with a macular vortex vein for 11 years. His refraction was -12D OU at age 10 years when the vein was first observed ophthalmoscopically in the left eye. Eleven years later, his myopia had progressed (4 diopters OD; 8 diopters OS), and the axial lengths were elongated (+1.8 mm OD; +2.7 mm OS). The macular vortex vein was dilated and tortuous. Indocyanine green angiography revealed the outflow route of this vein in the posterior pole, where both nasal and temporal posterior choroidal venous blood collected. Computed tomography showed that the vein left the eyeball directly and coursed along the optic nerve 5 mm posterior to the optic disc. A major collecting channel of posterior choroid outflow in some highly myopic eyes, a macular vortex vein may be formed at a relatively early age, and continue to enlarge, with elongation of axial length and progression of myopia.

Child↗

PubMed1997

Visual deprivation myopia with translucent and black goggles.

To study how different visual deprivation conditions influence the degree of myopia, chicks were reared under conditions of unilateral and bilateral visual deprivation with translucent and black goggles in environments of a 12-hour light/dark cycle and complete darkness. Two weeks after hatching, the refractive errors and axial lengths of the eyes were measured. The deprived eyes of the light/dark-reared chicks exhibited severe myopia both unilaterally and bilaterally as well as axial elongations. The dark-reared chicks exhibited slight myopia in the eyes with goggles and no significant axial elongation. The experiments suggest that different degrees of visual deprivation can also cause severe myopia, that myopia develops independently in each eye, and that a light/dark environment is required for severe myopia to develop.

Animals↗

PubMed1997

Coexistence of an autonomously functioning thyroid nodule in a patient with Graves' disease: an unusual presentation of Marine-Lenhart syndrome.

A 44-year-old woman developed hyperthyroidism due to the coexistence of Graves' disease and an autonomously functioning thyroid nodule (AFTN). Anti-thyrotropin receptor antibody (TRAb) was strongly positive (83.2%), and a thyroid scan initially showed diffuse uptake of Tc-99m pertechnatate in both lobes and further increased uptake in accordance with the right lobe nodule. The nodule in the right lobe was histologically diagnosed as thyroid follicular adenoma. After she was maintained in a euthyroid state by treatment with Methymazole (MMI), thyroid uptake of Tc-99m in the nodule became lower and was slightly suppressed by T3 administrations probably due to its dependence on TSH. Subtotal thyroidectomy was performed and she subsequently became euthyroid with negative TBII activity. It is concluded that she had a coexisting functioning nodule with Graves' disease (Marine-Lenhart syndrome) and that the nodule changed from hot to cool along with the anti-thyroid treatment, unlike usual cases of this syndrome showing a cold nodule on the initial imaging under the hyperthyroid state. Repeated Tc-99m pertechnatate thyroid scans were helpful in evaluating the reaction of MMI and TSH in both lesions separately in the present case.

Adenoma↗

PubMed1997

Simultaneous xenotransplantation of human Graves' thyroid tissue and autologous bone marrow cells in severe combined immunodeficient mice: successful reconstitution of human Graves' hyperthyroidism.

Human thyroid xenografts and the autologous bone marrow (BM) cells from five patients with Graves' disease (GD) were simultaneously xenografted into severe combined immunodeficient (SCID) mice to study the role of BM cells for the perpetuation of human GD autoimmunity and hyperthyroidism. All SCID mice engrafted with thyroid tissue (TH) alone, TH + autologous peripheral blood mononuclear cells, and TH + autologous BM cells produced similar amounts of human IgG; however, the production in TH + BM-engrafted mice peaked later than that of mice without BM. Production of thyroperoxidase antibody and thyroglobulin antibody in TH + BM-bearing SCID mice peaked in later weeks after xenografting than in those without BM. Moreover, human Graves' hyperthyroidism was actually reconstituted in TH + BM-transplanted mice; this was confirmed by (A) significantly higher levels and longer periods of secreting thyroid-stimulating antibody than those in mice without BM engraftment. (B) persistent hyperthyroxinemia up to the end of the experiment. (C) extremely high radioidine uptake of the xenografted thyroid tissue, and (D) histological findings of the maintenance of hyperplastic change of the xenografted thyroid epithelial cells. Human BM stem cells (CD34) were identified only in mice with TH + BM xenografts when analyzed by immunohistochemistry. In conclusion, (A) we have developed an animal model for human hyperthyroid GD by simultaneous xenotransplantation of GD thyroid tissue plus autologous BM cells into SCID mice, and (B) BM cells have a crucial role for perpetuating human GD autoimmunity and hyperthyroidism in this system.

Adult↗

PubMed1996

In vivo and in vitro association of retinoic acid with form-deprivation myopia in the chick.

The purpose of this study is to clarify the role of retinoic acid (RA) in the mechanism of form-deprivation myopia (FDM) in the chick. FDM was induced in two-day old chicks by placement of a translucent plastic goggle over one eye, with the contralateral eye used as a control. After 12 days, the chicks were euthanized. RNA was extracted from scleras in the posterior segments, transcribed into cDNA, and amplified by PCR with primers specific for retinoic acid receptor (RAR) beta. G3PDH was used as a reference gene for normalization. The effects of RA, with or without TGF-beta, on the proliferation of scleral chondrocytes and scleral fibroblasts from 17-day chick embryos were studied by use of a colorimetric assay, and the alkaline phosphatase activities of those cells also studied. Furthermore, RAR beta expression in response to RA in cultured scleral cells was studied. As a result, RT-PCR products of the expected sizes were obtained from scleras from the myopic and control eyes. Expression of RAR beta in the myopic scleras was significantly higher than that in the controls. The proliferation of scleral chondrocytes and scleral fibroblasts was inhibited by treatment with RA in a dose-dependent manner (in 10% FBS). In the presence of TGF-beta (in 0.5% FBS), RA treatment stimulated the proliferation of scleral chondrocytes but inhibited the proliferation of scleral fibroblasts. RA induced alkaline phosphatase activities in both the scleral chondrocytes and scleral fibroblasts. RAR beta expression was induced by RA in cultured scleral cells. These results demonstrate that RA appears to play a role in the mechanism of FDM in the chick. However, it is also possible that the changes in the expression of RAR beta were secondary events related to other mechanisms responsible for ocular enlargement.

Alkaline Phosphatase↗