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Biomedical subjects

T Hida

Publications and source records attributed to T Hida.

At least 55 records · Page 3Linked to original sources

Monoamine oxidase activity in noradrenaline neurons of the locus coeruleus of the rat. A double-labeling histochemical study.

The aim of the present study is to examine whether noradrenergic neurons of the locus coeruleus (LC) of the rat contain monoamine oxidase (MAO) activity. Sections were processed initially for MAO enzyme histochemistry using tyramine as a substrate, followed by fluorescence immunohistochemistry for tyrosine hydroxylase (TH). In the LC, virtually all TH-immunoreactive neurons (i.e., noradrenergic neurons) were also positive for MAO. No MAO activity was found in any TH-negative neurons. Neurons in the LC have previously been shown to form dopamine during noradrenaline biosynthesis and to produce serotonin from exogenously administered l-5-hydroxytryptophan. Moreover, dopamine- and serotonin-degrading MAO activity has also been found in LC neurons. Therefore, our results indicate that MAO activity is localized within noradrenergic neurons in the LC and is likely involved in the degradation of dopamine that is endogenously synthesized, and also in the elimination of serotonin that is produced from exogenous precursors.

Animals↗

Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas.

Cyclooxygenase (COX)-2 expression was immunohistochemically examined in 59 human lung cancers as well as in normal and premalignant lung specimens. In contrast to scattered weak reactivity seen in normal peripheral airway epithelial cells, markedly up-regulated COX-2 expression was detected in about one-third of atypical adenomatous hyperplasias and carcinoma in situ specimens, and a significant increase in COX-2 expression was observed in 70% of invasive adenocarcinoma cases. Interestingly, the proportion of adenocarcinoma cells with marked COX-2 expression was much greater in lymph node metastases than in the corresponding primary tumors. In contrast, small cell carcinomas showed virtually negligible expression, and squamous cell carcinomas showed infrequent and low expression. These findings suggest that an increase in COX-2 expression may be associated with the development of adenocarcinomas and possibly with acquisition of an invasive and metastatic phenotype.

Adenocarcinoma↗

Syntheses and structure-activity relationships of novel retinoid X receptor agonists.

As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, generated by introducing a polar N atom into the hydrophobic part of the retinoid skeleton, showed high binding affinity to RXRs. Addition of fluorine at the 6-position of the 2,4,6-trienoic acid moiety afforded compounds which elicit potent and selective transactivation of the RXRs. Compound 14b (ER-35794), which possesses an ethyl substituent at the 7-position and fluorine at the 6-position of the triene moiety, is one of the most potent and selective RXR agonists reported to date.

Animals↗

Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene.

We investigated the XLRS1 gene in Japanese patients with retinoschisis (RS). All exons of the XLRS1 gene were sequenced in 14 males, including a pair of monozygotic twins, from 11 individual families with RS and five of their mothers who are asymptomatic but diagnosed as carriers. Six kinds of missense mutations and a nonsense mutation, including six novel mutations, were detected in all 14 patients and carriers. Mutations in the XLRS1 gene are also responsible for RS in non-Caucasian patients. Most Japanese RS cases are caused by an XLRS1 gene defect. A novel mutation, Glu72Lys, was found in four families, suggesting a common mutation in the Japanese population. Clinical features of RS patients with both the Glu72Lys and Pro193Leu mutations indicate that a genotype-phenotype correlation is not recognized in RS.

Eye Diseases, Hereditary↗

Glycosaminoglycan and collagen distribution in the developing human vitreous.

BACKGROUND: We determined the distribution of glycosaminoglycans and collagens in the developing human vitreous. METHODS: Eighty human eyes from 5 gestational weeks to 2 postnatal years of age were used. Glycosaminoglycan components were determined by enzyme digestion with hyaluronidase or chondroitinase AC and ABC and immunohistochemistry for chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate. Collagen distribution was determined by immunohistochemistry for types I, II, and III collagens. RESULTS: Enzyme digestion showed that throughout development hyaluronic acid is the main glycosaminoglycan in the vitreous and in the extraocular space at 5-7 gestational weeks. Both areas were filled with mesenchymal cells. Immunohistochemistry showed chondroitin-6-sulfate in the vitreous between 6 and 40 gestational weeks, and chondroitin-4-sulfate between 12 and 40 gestational weeks. Hyaluronic acid and chondroitin sulfate appeared in the retina and around the hyaloid vessels at 12-40 weeks. Immunohistochemistry showed type III collagen in the vitreous and around the mesenchymal cells at 5-7 weeks that was replaced by type II collagen after 8 weeks. CONCLUSIONS: Hyaluronic acid is the major glycosaminoglycan in the vitreous throughout development, except for the transient appearance of chondroitin sulfate at 6-40 gestational weeks. Type III is the main collagen in the early developing vitreous that converts to type II collagen at 8 weeks. The primary and secondary vitreous has the same components as these macromolecules. These vitreous glycosamino-glycans and collagens seem to be produced by mesenchymal cells at an early stage and by the retina and hyaloid vessels during middle and late development.

Adolescent↗

Practical synthesis of androgen: the efficient transformation of 17-oxo group to 17 alpha-hydroxy group.

The present report describes the improved transformation of the 17-oxo group in 3 beta-acetoxy-5 alpha-androstan-17-one to a 17 alpha-hydroxy group. A mixture of 17 alpha-acetoxy and 16-ene compounds, which are usually produced by the standard synthetic route, were treated with peracetic acid (epoxidation of the 16-ene compound) and then sodium borohydride-sodium hydroxide (reduction-hydrolysis) to give the desired 17 alpha-hydroxy compound in much better yield than that in previous reports. Recrystallization of the crude product with cyclohexane-methanol gave the pure compound in 54% yield (total yield from starting ketone).

Androgens↗

A novel retinoic acid receptor (RAR)-selective antagonist inhibits differentiation and apoptosis of HL-60 cells: implications of RARalpha-mediated signals in myeloid leukemic cells.

Retinoic acid (RA) induces HL-60 cells to differentiate terminally into mature granulocytes, which subsequently die by apoptosis. The biological effects of RA are mediated by two distinct families of transcription factors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RARs and RXRs form heterodimers and regulate retinoid-mediated gene expression. We have recently developed a novel RAR-selective antagonist (ER27191) which prevents RAR activation by retinoids. Using this RAR-selective antagonist, and RXR and RAR agonist, we demonstrate the RAR-mediated signaling pathway is important for differentiation and apoptosis of myeloid leukemic cells. Simple activation of RXRs is not sufficient to induce apoptosis of the cells. Interestingly, the combination of the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and apoptosis of HL-60 and NB4 cells, whereas the RAR antagonist completely blocked all-trans RA-induced differentiation and apoptosis of the cells. Additional experiments showed that levels of BCL-2 protein decreased during differentiation of myeloid leukemic cells. Furthermore, HL-60 cells transduced with a bcl-2 expression vector showed the same differentiation response to retinoids as did parental HL-60 cells even though apoptosis was inhibited in these bcl-2-transduced cells, suggesting that differentiation and apoptosis are regulated independently in myeloid leukemic cells.

Alitretinoin↗

[Characteristics of retinal detachment in eyes with choroidal colobomas].

We reviewed 6 eyes of 6 patients (1 male and 5 females) with retinal detachment associated with choroidal coloboma. Three of these 6 eyes had visible retinal breaks within or at the margin of the coloboma. In one eye, no retinal breaks were noted before or during vitreous surgery, and shallow retinal detachment was localized in the posterior fundus. One eye with bullous retinal detachment with retinal breaks within the coloboma had been having serous retinal detachment localized in the nasal area close to the optic nerve head. In all of these five eyes; vitrectomy, relaxing retinotomy inside the coloboma close to its edges, and cyanoacrylate retinopexy resulted in successful reattachment of the retina. Schisis-like separation similar to that in pit-macular syndrome was noted in the posterior retinal in one eye which had no visible retinal break. Non-rhegmatogenous retinal detachment may exist in association with choroidal colobomas.

Adolescent↗

CD44 expression in the developing human retina.

BACKGROUND: CD44, the transmembrane adhesion molecule, is expressed in the fetal brain and supposed to mediate neuroglial, interactions. We evaluated the expression and distribution of CD44 in the developing human retina. METHODS: Four developing human eyes were evaluated at 6, 10, 16, and 21 weeks of gestation, as well as the eyes of one infant and four adults. Frozen sections were immunohistochemically stained with monoclonal antibodies to three human CD44 clones (BU52, F10-44-2, and DF1485) and to vimentin, and antiserum to glial fibrillary acidic protein (GFAP). Specimens were evaluated by light and electron microscopy. RESULTS: Positive immunostaining for CD44 was first detected at 21 weeks of gestation in the longitudinal fibers that extended from the inner to the outer limiting membrane and around capillary vessels with the simultaneous expression of vimentin and GFAP. Immunoelectron microscopy demonstrated the presence of CD44 on the surface of Müller cells and astrocytes. CD44 was faintly seen in the Müller cells in the periphery and definitely present in the astrocytes in the infant and adult retinas. CONCLUSION: CD44 was expressed in Müller cells at a late stage of fetal development and in the fetal, infant, and adult astrocytes, which suggests that it is important in the morphogenesis and homeostasis of the neural retina.

Adult↗

PACAP hybrid: a new PACAP receptor antagonist.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) hybrid, a synthetic antagonist, was investigated on NIH/3T3 cells containing PACAP receptor (R) splice variants (SVs). PACAPhybrid inhibited 125I-PACAP-27 binding to NIH/3T3 cells stably expressing PACAP-R basic, SV-1, SV-2 or SV-3 with an IC50 of 1000 nM. PACAPhybrid antagonized the ability of PACAP-27 to elevate cAMP regardless of the PACAP-R SV used. PACAP was more efficacious at increasing cytosolic Ca2+ in NIH/3T3 cells containing PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in cytosolic Ca2+ caused by PACAP-27 regardless of the PACAP-R SV used. PACAP was more potent at elevating c-fos mRNA using NIH/3T3 cells transfected with PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in c-fos mRNA caused by PACAP-27. These data suggest that PACAPhybrid is a useful PACAP receptor antagonist for PACAP-R SVs.

3T3 Cells↗

[Proliferative vitreoretinopathy treated with daunorubicin].

Nine eyes with severe proliferative vitreoretinopathy underwent vitrectomy and infusion of Daunorubicin to prevent reproliferation. In 5 eyes (56%) the retina was reattached. In 4 eyes redetachment occurred because of reproliferation or incomplete sealing of the break. After a second vitrectomy, complete reattachment of the retina was obtained eventually in all eyes including one eye with silicone oil tamponade. As postoperative complications, conjunctival dehiscience occurred in 3 eyes. In two of the 3 eyes scleral buckling occurred, and orbital cellulitis occurred in one eye. Daunorubicin seemed to be effective to suppress reproliferation, but care should be taken to avoid postoperative complications.

Adolescent↗

[Posterior segment complications after macular hole surgery].

Fifty-three patients with stage III or stage IV idiopathic macular holes who underwent vitrectomy were reviewed. Posterior segment complications were noted in 20 (38%) of patients. These included peripheral retinal breaks (21%), peripheral visual field loss of unknown etiology (8%), rhegmatogenous retinal detachment caused by peripheral retinal break (6%), late reopening of the hole (4%), and retinal pigment epithelium loss under the hole (4%). The final visual acuity was two lines or more worse than preoperative visual acuity in 10% of these complicated eyes and in 9% of eyes without posterior segment complications. Patients with peripheral retinal breaks or retinal detachment had significantly shorter duration of macular hole symptoms (p < 0.01) than those without these complications. Posterior segment complications after vitrectomy for macular hole appear to be more common than expected, but the effect of such complications on final visual outcome was not significant.

Aged↗

Subretinal fluid drainage with the erbium:YAG laser in rabbit eyes.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of the erbium:yttrium-aluminum-garnet (Er:YAG) laser for choroidotomy as a means of performing external drainage of subretinal fluid with less risk of choroidal bleeding. MATERIALS AND METHODS: The authors tested this application in a rabbit model of retinal detachment by evaluating the effects of Er:YAG laser energy on the bare choroid at various energy settings (1, 2, 3, or 5 mJ/pulse) and repetition rates (2, 4, 10, or 30 Hz). RESULTS: Although the choroid was not perforated at low energy and frequency settings, choroidotomy was successfully achieved as energy and repetition rate were increased. Through higher energy levels per pulse and higher repetition rates, choroidotomy was achieved at lower total energy levels. No retinal damage was detected after laser choroidotomy. Choroidal bleeding was noted in 2 of 97 eyes; however, no subretinal hemorrhage occurred. CONCLUSION: These results indicate that the Er:YAG laser may be a clinically useful tool for retinal reattachment surgery.

Animals↗

[Elucidation of the mechanism of retinal degeneration and regeneration and the prospects for its clinical application].

In order to obtain the basic knowledge necessary to develop therapeutical intervention for blindness due to the damaged retina and optic nerve, the mechanism of retinal degeneration and regeneration in an amphibian model, Cynops pyrrhogaster, was studied. In the retinal degenerative process following enucleation and reimplantation of the eye ball, evidence was found for active cell death of neural retinal cells. As the degeneration proceeded, Musashi, an ribonucleic acid (RNA)-binding protein, started its expression in the daughter cells of proliferating retinal pigment epithelium (RPE) cells, messenger RNA (mRNA) expression of proneural genes with basic helix-loop-helix motif was then detected in the newly developing retina. These results suggest that transdifferentiation of RPE cells to neural retina involves at least partial cascade, if not entirely, of neural induction from uncommitted ectodermal tissue. Search for genes that are required for transdifferentiation of RPE cells to neural retinal cells, in addition to those mentioned above, will provide the basic knowledge for successful retinal transplantation and retinal regeneration in higher vertebrates.

Amphibians↗

[Clinical study of occupational uroepithelial cancer].

We studied 438 persons who were engaged in the production and use of aromatic amines (benzidine sulfate, beta-naphthylamine, alpha-naphthylamine and dianisidine). Among these 438 persons, 88 new cases of occupational uroepithelial cancer had occurred from 1949 to 1995. The incident rate of occupational uroepithelial cancer was 20.1%. The average exposure period of these 88 cases to the aromatic amines was 7.40 years (range, 0.75-26.75), and the incidence rate of tumors increased with the length of exposure to aromatic amines. The average latent period was 26.79 years (range, 1.33-48.50), and the average age of first onset was 52.59 (range, 24-79). Recently it has been determined that the longer the latent period, the older the age of first onset. Of these 88 cases, the tumor sites were bladder in 67 cases (76.1%) and upper urinary tract (renal pelvis and/or ureter) in 5 cases (5.7%). The other 16 cases (18.2%) were the bladder and upper urinary tract. The screening examination for chemical workers using urinary cytology was begun in 1962. In our cases, urine cytology was a useful method for diagnosing occupational uroepithelial cancer. As for initial treatment of the 88 cases, transurethral surgery was most frequently performed, that is on 58 cases (65.9%). However, eight cases (9.1%) had to undergo a total nephroureterectomy, and six cases (6.8%) had a total cystectomy. Recurrence was observed in 61 cases (69.3%) out of the 88 patients with an average of 1.81 times. The other organic cancers developed in 39 cases (8.9%) out of 438 workers who were exposed to aromatic amines and in 8 cases out of 88 patients (9.1%). Prognosis of the 88 patients is that, the number of alive and dead is 51 (58.0%) and 37 (42.0%) respectively on December 31, 1995. Twenty-eight patients (31.8%) died of uroepithelial cancer, and five patients (5.7%) died of other organic cancers. The survival rates of 5, 10, 15 and 20 years was 87.9%, 74.0%, 65.9% and 56.3%, respectively. From these results, patients with occupational uroepithelial cancer and workers who are exposed to aromatic amines should undergo long term observation.

2-Naphthylamine↗

Breast cancer growth is inhibited by vasoactive intestinal peptide (VIP) hybrid, a synthetic VIP receptor antagonist.

Breast cancer vasoactive intestinal peptide (VIP) receptors were characterized. Using in vitro autoradiographic techniques, 125I-labeled VIP bound with high affinity to breast biopsy sections. 125I-labeled VIP bound specifically to give breast cancer cell lines examined using receptor-binding techniques. Specific 125I-labeled VIP binding to MDA-MB-231 cells was inhibited with high affinity by VIP and pituitary adenylate cyclase-activating polypeptide (IC50, = 2 nM) and with moderate affinity by the VIP hybrid (IC50 = 0.5 microM). VIP elevated the cAMP in a dose-dependent manner, and VIP hybrid (10 microM) inhibited the increase in cAMP caused by VIP. Using Northern blot analysis, VIP (10 nM) stimulated c-fos and c-myc mRNA, and the increase caused by VIP was reversed by the VIP hybrid. The VIP hybrid inhibited breast cancer growth in vitro and in vivo using nude mice bearing breast cancer xenografts. These data suggest that the VIP hybrid is a breast cancer VIP receptor antagonist.

Animals↗

Retrospective survey of surgical outcomes on rhegmatogenous retinal detachments associated with atopic dermatitis.

OBJECTIVE: To determine the clinical features and surgical outcomes of retinal detachment associated with atopic dermatitis. METHODS: One hundred twenty-one eyes of 98 patients with atopic dermatitis and rhegmatogenous retinal detachment were surgically treated and followed up for 1 year or longer. Fundus examination data on retinal breaks and detachment, and follow-up data on anatomic reattachment were obtained and compared between phakic and aphakic eyes using the chi 2 test. RESULTS: Breaks were often multiple and located at the ora serrata (72%) and in the ciliary epithelium (15%). Irregularly shaped breaks (13.5%) and giant breaks (16%) also were seen. Most detachments (71%) were localized and shallow. No significant difference was identified with or without a history of cataract surgery. The prognosis after the initial surgery (reattachment rate, 72%) was unfavorable because of new break formation, but the results of reoperation (reattachment rate, 93%) were as successful. CONCLUSIONS: Patients with atopic dermatitis may have an abnormality in the anterior retina and ciliary epithelium that predisposes to retinal detachment. Findings suggest a possible traumatic trigger and the need to perform an encircling scleral buckle procedure with widespread retinopexy initially in these patients.

Adolescent↗