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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 289 records · Page 16Linked to original sources

A mild progression type of naphthalene-induced cataract in brown-Norway rats.

Naphthalene-induced rat cataract is a useful experimental cataract--however, because of its short survival period, studies using this model have been for limited purposes. Based on the consideration that the short survival might be caused by systemic toxicity of an overdose of naphthalene administration (1 g/kg body weight every other day), the authors successfully established a naphthalene-induced cataract with mild progression in Brown-Norway rats. The naphthalene administration proposed is to initially administer 0.5 g/kg and after a 1-week interval 1 g/kg of 10% naphthalene once or twice a week through a stomach tube. While the type of lens opacification induced in the two groups administered once and twice a week, respectively, was the same as that seen by the previous administration method, the progression of lens opacification seen in the groups showed a dose-dependent increase. The survival rate in the rats given naphthalene every other day according to the old method was 50% at the 6th week and 0% at the 9th week. Survival of the two new groups was 70 and 60% at the 30th week, respectively. This new type of naphthalene-induced rat cataract should be a suitable model for long-term observations.

Animals↗

Growth inhibition of human glioma cells by superinduced human interferon-beta.

Superinduction of human interferon-beta (HuIFN-beta) from human glioma cells has greater cytotoxicity than purified HuIFN-beta derived from fibroblasts. However, superinduction requires several reagents like polyI:polyC, cycloheximide, and actinomycin D, which may contaminate the conditioned medium and obscure the effect of superinduced HuIFN-beta. The present study used minimum doses of polyI:polyC and cycloheximide without actinomycin D to superinduce HuIFN-beta. The superinduced HuIFN-beta was purified by passing the medium through molecular sieve column chromatography. Fractionation of the eluate provided semipurified superinduced HuIFN-beta which demonstrated a growth inhibitory effect against both the U251-MG autologous human glioma cell line and the SK-MG-1 homologous glioma cell line. This effect was neutralized by addition of anti-HuIFN-beta monoclonal antibody (YSB-1). In a separate experiment, combinations of superinduction reagents were found not to have growth inhibitory effects because all inhibition in superinduced medium was completely neutralized by YSB-1. Superinduced HuIFN-beta has a pure growth inhibitory effect on both autologous and homologous glioma cells, so may affect autocrine secretion of cytokines.

Antibodies, Monoclonal↗

Expression of intercellular adhesion molecule 1 on pancreatic beta-cells accelerates beta-cell destruction by cytotoxic T-cells in murine autoimmune diabetes.

Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) by being involved in the extravasation of lymphocytes from the circulation into the inflamed pancreas. However, the mechanism of beta-cell destruction by which expression of ICAM-1 on beta-cells may facilitate adhesion of effector cells still remains to be elucidated. Several lines of evidence suggest that this adhesion molecule is involved in the destruction of pancreatic beta-cells by killer lymphocytes in the NOD mouse, which shows an autoimmune diabetic syndrome similar to that of human IDDM. Immunohistochemical study under light microscopy demonstrated that all of the mononuclear cells infiltrating the islets strongly expressed ICAM-1 and leukocyte function-associated antigen 1 (LFA-1), a counterreceptor of ICAM-1, whereas ICAM-1 expression on islet cells was not apparent. However, immunohistochemical staining under electron microscopy revealed that islet beta-cells adjacent to infiltrating lymphocytes were clearly stained by an anti-ICAM-1 monoclonal antibody (mAb). Flow cytometric analysis showed that the ICAM-1 expression on NOD islet cells and NOD-derived insulinoma cells (MIN6N8a) was inducible by interferon (IFN)-gamma or tumor necrosis factor-alpha. These cytokines had an additive effect on the ICAM-1 induction. Susceptibility of MIN6N8a cells to lysis by a NOD islet-derived CD8+ cytotoxic T-cell clone was greatly enhanced by IFN-gamma pretreatment, and this enhancement was abolished by anti-ICAM-1 and anti-LFA-1 mAbs. When both mAbs were administered into NOD mice with spontaneous or adoptively transferred diabetes, the development of diabetes was significantly prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulation of mucosal glutathione and angiogenesis: new mechanisms of gastroprotection and ulcer healing by sucralfate.

BACKGROUND: Among the endogenous mediators (e.g., PG, SH) of gastroprotection, so far only PG was implicated in the mechanism of acute gastroprotection by sucralfate. Angiogenesis, which is stimulated by bFGF, is a recently recognized element in ulcer healing, and sucralfate binds bFGF in vitro and in vivo. METHODS: In fasted rats the gastric mucosal concentration of GSH and protein SH was measured at 30, 60, 120, and 240 min after a single gastroprotective dose of sucralfate. In normally fed rats, angiogenesis was measured in the subcutaneous sponge assay 7 days after the implantation of sponges containing sucralfate and/or bFGF. RESULTS: A gastroprotective dose of sucralfate time-dependently increased GSH concentration in the gastric mucosa. Sucralfate alone accelerated angiogenesis, which was significantly enhanced by combination with an ineffective dose of bFGF in the subcutaneous sponge assay. The same dose of sucralfate combined with an angiogenic dose of bFGF also resulted in synergistic stimulation (e.g., more than fivefold) of angiogenesis. CONCLUSIONS: It appears that elevated mucosal GSH concentration may represent a new factor in the mechanism of acute gastroprotection by sucralfate, and stimulation of angiogenesis is one of the mechanisms of ulcer healing by sucralfate.

Animals↗

[Clinical experience with the artificial urinary sphincter AMS 800 for male incontinence].

BACKGROUND: The aim of this study is to evaluate the therapeutic efficacy of artificial urinary sphincter AMS 800 implants for male patients with urinary incontinence. METHODS: Eleven male patients with urinary incontinence were treated by implantation of the artificial urinary sphincter AMS 800 between 1988 and 1992. Patient age at the surgery ranged from 14 to 79 years, with a mean age of 58 years. At presentation, 9 patients (82%) had true incontinence and 2 had overflow incontinence, and medical treatments and/or surgical procedures (Teflon injections in 2 and Sling procedure in 1) had been attempted previously elsewhere in all patients. The etiologies of incontinence were post-prostatectomy (transurethral resection in 4 and radical retropubic prostatectomy in 4) in 8 patients (73%) and myelomeningocele, spinal cord injury, pelvic trauma in one each. There were 5 patients with abnormal cystometrogram, and 2 of them were performing intermittent self catheterization. Vesicoureteral reflux was determined in 2 patients preoperatively, which were surgically corrected one year before AMS800 implant in a patient and simultaneously in another patient. The cuff was placed around the bulbous urethra (9), pendulous urethra (1) or bladder neck (1). The device was activated 6 weeks post implantation, and the assessment of therapeutic effects was started 2 weeks after activation. RESULTS: Follow up ranged from 3 weeks to 75 months, with a mean of 56 months, if 3 cases done explantation due to periprosthetic infections were excluded. After AMS 800 implantation 5 patients (45%) were completely continent, 4(36%) required the use of not more than 1 pad per day, while a patient was not satisfied with the results and another patient was not definitive because of early explantation before device activation. Hence complete or near complete continence was achieved in 9 patients (81%). A patient is performing intermittent self catheterization in conjunction with the AMS 800 without any complications up until now. There were 3 periprosthetic infections (27%) associated with 2 cuff erosions, that consequently required explantation. Besides periprosthetic infection, neither complications nor mechanical device failures was experienced. CONCLUSION: In conclusion, the AMS 800 artificial urinary sphincter was safe with reasonable mechanical reliability and offered acceptable and satisfactory urinary control to the selected patients with incontinence.

Adolescent↗

Myxoma of the conjunctiva: a case report and a review of the literature.

A rare case of conjunctival myxoma is reported. A painless tumor was noted in the left bulbar conjunctiva of an 80-year-old woman. The extirpated tumor, 12 x 10 mm, was hypocellular and composed of spindle-shaped or stellate tumor cells. The tumor stroma showed extensive myxomatous changes. Alcian blue stain with hyaluronidase digestion revealed that the matrix contained rich amounts of hyaluronidase-sensitive acid mucopolysaccharides. Immunohistochemically, the tumor cells were positive for vimentin and alpha-smooth muscle actin, suggesting a fibroblastic or myofibroblastic cell phenotype. A review of the literature revealed the rare incidence and invariable benign behavior of conjunctival myxoma.

Actins↗

Histopathological study of microspherophakia in the Weill-Marchesani syndrome.

A surgically obtained lens from a 66-year-old man with the Weill-Marchesani syndrome was examined histopathologically by light microscopy, transmission electron microscopy and scanning electron microscopy. The lens was diffusely opaque and brown. It was microspherophakic in appearance, 6.0 mm in equatorial diameter and 4.8 mm in anteroposterior diameter. The lens fibers were well preserved, and ran circularly in the cortex and elliptically in the fetal nucleus. The lens fibers had undergone hyaloid degeneration in the area from the deep cortex to the superficial portion of the adult nucleus. Hyaloid degeneration also extended from the anterior to the posterior pole and was more marked in the equator. The distribution of lens fibers suggested that microspherophakia had developed postnatally. It is surmised that later changes in the shape of the lens affected the lens fibers, inducing hyaloid degeneration.

Abnormalities, Multiple↗

[Surgical effects of trabeculotomy after long-term topical antiglaucoma medications].

We retrospectively analyzed the effects of long-term topical antiglaucoma therapy on the results of trabeculotomy. We studied 83 eyes with 76 primary open angle glaucoma and 7 eyes with capsular glaucoma, each of which had undergone trabeculotomy alone and none of which had a history of laser trabeculoplasty or glaucoma surgery. The outcome of trabeculotomy was assessed after a minimum follow-up of 12 months. Using a life-table method, there was no significant difference in the outcome of trabeculotomy between groups divided by duration and type of preoperative topical therapy. There was not statistically significant difference in the intraocular pressure reduction between the groups of long or short duration of topical therapy. We concluded that the duration and type of topical antiglaucoma medications had no significant effect on the outcome of trabeculotomy.

Administration, Topical↗

Fast oscillations of the electro-oculogram in a series of normal subjects.

Using a newly devised automated electro-oculograph, Nidek EOG-2, the fast oscillations (FOs) of the electro-oculogram were recorded in the 120 eyes of 60 normal subjects. We evaluated the normal means and variability of FO parameters, namely the "Rf" value, which is the average ratio in percentage of the maximum amplitude in the dark period (AD)/the minimum amplitude in the light period (AL), and the "df" value, which is the average difference between AD and AL during the FO measurement. No correlation with age was noted in the "Rf" value, although the lowest mean value of the "df" was detected in the twenties. Regarding sex, the mean levels of the "Rf" and "df" for female subjects were statistically higher than those for male subjects in the younger and global age groups. Some hormonal factor which can stimulate the metabolic activity of the retinal pigment epithelium might have caused this sexual difference.

Adult↗

[Prenatal detection of the growth-retarded fetuses with a serious risk of adverse perinatal outcome by uterine artery Doppler flow velocimetry: a prospective study].

Our objective was to evaluate the predictive value of uterine artery Doppler flow velocimetry with regard to a serious risk of adverse perinatal outcome in growth-retarded fetuses. A prospective comparative study of pregnancies complicated with growth-retarded fetus with normal and abnormal uterine artery blood flow was performed. Ninety-three pregnancies were assessed by Doppler flow velocimetry in terms of the resistance index at 27-36 weeks. The relative risks (95% Confidence Interval) in 52 pregnancies with abnormal uterine artery blood flow compared with 41 pregnancies with normal uterine artery blood flow were as follows: Premature delivery: 2.29 (1.32-3.97), birth weight < 2,000g: 2.94 (1.74-4.97), cesarean section for fetal distress: 2.57 (1.30-5.05), admission to NICU: 3.27 (1.60-6.69). The findings in this study suggest that abnormal uterine artery blood flow is associated with a serious risk of adverse perinatal outcome in a pregnancy complicated with a growth-retarded fetus. Doppler flow velocimetry of the maternal uterine artery is useful for determining the clinical management of a pregnancy complicated with a growth-retarded fetus.

Adult↗

Prevention of autoimmune type I diabetes in biobreeding (BB) rats by a newly established, autoreactive T cell line from acutely diabetic BB rats.

An autoreactive T cell line, BNY-2, was established from lymphocytes isolated from the islets of acutely diabetic BioBreeding (BB) rats after continuous stimulation of the isolated lymphocytes by irradiated lymph node cells. Flow cytometric analysis showed that BNY-2 cells were positive for CD4 and CD5 and were negative for CD8 and RT6, indicating that these cells were phenotypically Th cells rather than cytotoxic T cells. mAbs against rat MHC class II Ags (anti-RT1.D) blocked the proliferation response of BNY-2 cells, suggesting that these cells recognize the MHC class II Du molecule. When splenic T lymphocytes from diabetes-prone BB rats were stimulated by Con A in the presence of irradiated BNY-2 cells or irradiated lymph node cells, the BNY-2 cells had a significant suppressive effect on splenic T cell proliferation, whereas lymph node cells had no effect. When we injected diabetes-prone BB rats i.v. at 30 and 60 days of age with activated BNY-2 cells, the incidence of diabetes was significantly reduced compared with that seen in saline-injected control rats (diabetic incidences were 12 and 80%, respectively). On the basis of these observations, we conclude that autoreactive BNY-2 T cells, established from the pancreatic islets of acutely diabetic BB rats, can prevent the development of autoimmune diabetes in the diabetes-prone BB rat by an immunosuppressive effect.

Animals↗

Prevention of recurrent diabetes in syngenic islet-transplanted NOD mice by transfusion of autoreactive T lymphocytes.

Islet transplantation has been considered to be one of the best methods for the cure of type I diabetes, but transplanted islets are eventually destroyed by the host's cell-mediated autoimmune responses unless immunosuppressive agents are given. This investigation was initiated to develop a method for the prevention of beta cell destruction in transplanted islets without the use of immunosuppressive drugs. We have recently cloned CD4+ autoreactive T cells (NY1.1 and NY4.2) from lymphocytes infiltrating the pancreatic islets of nonobese diabetic (NOD*) mice and have shown that these cells respond to self MHC class II determinants. When the T cell clones (10(7) cells of either NY1.1 or NY4.2) were transfused into acutely diabetic NOD mice 2 to 3 days before transplantation of syngenic islets (400) into the subrenal space, the transplanted islets were not destroyed, and the animals maintained normoglycemia over 100 days without insulin treatment. In contrast, NOD mice that received syngenic islets (400) without the transfusion of an autoreactive T cell clone showed a recurrence of diabetes and massive mononuclear cell infiltration of the grafted islets within 17 days. On the basis of these observations, it is concluded that CD4+ autoreactive T lymphocytes can prevent the recurrence of insulitis and development of diabetes in pancreatic islet-transplanted NOD mice, without treatment with immunosuppressive drugs.

Animals↗

Expression cloning of a novel alpha 1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis x carbohydrate determinants in leukocytes.

The sialyl Lewis x (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)Glc-NAc) determinants serve as ligands in the selectin-mediated adhesion of leukocytes to activated endothelium or platelets. In our efforts to identify glycosyltransferases involved in the biosynthesis of those ligands, we achieved expression cloning of a novel human alpha 1,3-fucosyltransferase termed Fuc-TVII from a THP-1 cDNA library by enrichment of the Namalwa cells highly expressing that determinant with a fluorescence-activated cell sorter. Expression of the COOH-terminal catalytic domain of Fuc-TVII showed an alpha 1,3-fucosyltransferase activity for a type II oligosaccharide with a terminal alpha 2,3-linked sialic acid among various acceptors, consistent with that in vivo acceptor specificity. Alignment of the primary sequences of five alpha 1,3-fucosyltransferases and assignment of the chromosomal location of Fuc-TVII gene, together with that acceptor specificity, indicate that Fuc-TVII consists of a unique class of the alpha 1,3-fucosyltransferase family. Determination of the expression levels of these alpha 1,3-fucosyltransferases in various cells revealed that both Fuc-TVII and a myeloid fucosyltransferase Fuc-TIV were significantly expressed in myeloid lineage cells. Fuc-TVII-transfected Namalwa cells exhibited significant binding to E-selectin in contrast to little binding of the Fuc-TIV-transfected cells. These results suggest that Fuc-TVII may participate in the biosynthesis of the selectin ligands.

Antibodies, Monoclonal↗

A novel cytosolic component, p40phox, of respiratory burst oxidase associates with p67phox and is absent in patients with chronic granulomatous disease who lack p67phox.

Cytosolic components of human neutrophils, p47phox and p67phox, deficiencies of which lead to chronic granulomatous disease (CGD), potentiate respiratory burst oxidase translocating from cytosol to membrane upon cell stimulation. In this report we describe a novel cytosolic component, p40phox, which consistently behaves with p67phox through immunoprecipitation and column works, and is missing in patients with CGD who lack p67phox. Although actin has been reported to be involved in O2- generation, the p40phox profile did not correspond to that of actin. The tight association between p40phox and p67phox was not affected by treatment with a mixture of deoxycholate and Nonidet P-40, until subjected to SDS-PAGE. Addition of recombinant p67phox to cytosol did not produce any additional p40phox in the immunoprecipitate, unlike the additive increment in the band of p67phox. These results suggest that p40phox forms a complex with p67phox in a molar ratio of 1:1, without any free p40phox in the cytosol.

Cell Membrane↗

Evidence for the role of CD8+ cytotoxic T cells in the destruction of pancreatic beta-cells in nonobese diabetic mice.

CD8+ islet cell-specific CTL lines and clones were established from lymphocytes infiltrating the pancreatic islets of acutely diabetic nonobese diabetic (NOD) mice from two subcolonies (NOD/Yn and NOD/Lt). CTL from NOD/Yn mice were predominantly cytotoxic against H-2b+ islet cells and to a lesser extent against H-2d+ islet cells. On the other hand, CTL from NOD/Lt mice were cytotoxic against H-2d+ but not against H-2b+ islet cells. Three of four CTL clones derived from NOD/Yn mice were H-2Db restricted, whereas two of two CTL clones derived from NOD/Lt mice were H-2Kd restricted. However, all of the H-2Kd restricted T cell clones expressed the same TCR, regardless of the NOD subcolony from which they were derived, compatible with a restricted repertoire. When two representative CTL clones were transferred into irradiated young NOD mice, neither induced insulitis or diabetes. However, transfer of these clones, together with CD4(+)-rich NOD splenocytes depleted of CD8+ T cells, caused severe insulitis and diabetes. When recipient NOD mice were treated with anti-CD4 mAbs, none of the mice developed insulitis or diabetes. Most of the irradiated NOD mice that received CD8-depleted splenocytes alone did not become diabetic. Through these studies we show that CTL clones can destroy pancreatic beta-cells as final effectors but that these clones require signals from CD4+ T cells to effect beta-cell damage.

Amino Acid Sequence↗

Surgical results of trabeculotomy ab externo for developmental glaucoma.

OBJECTIVE: To elucidate long-term surgical outcome of trabeculotomy ab externo in the treatment of developmental glaucoma. PATIENTS: Included in this retrospective study are 116 eyes of 71 patients with developmental glaucoma. We classified patients into three groups based on their age: congenital (33 eyes), existing before age 2 months; infantile (31 eyes), occurring from ages 2 months to 2 years; and juvenile (52 eyes), age 2 years or older. RESULTS: A life-table analysis showed that the total success probabilities at 5 and 10 years with one or more trabeculotomy ab externo operations were, respectively, 92.5% +/- 2.7% and 76.5% +/- 6.2%. The success probability of patients with congenital glaucoma (60.3% +/- 15.9%) was significantly lower than it was for those with infantile (96.3% +/- 3.6%) or juvenile (76.4% +/- 7.5%) glaucoma (P < .01 for both). CONCLUSIONS: Surgical results of trabeculotomy ab externo remain effective for a long time. Congenital glaucoma has the worst prognosis, and infantile glaucoma has a better prognosis than does juvenile glaucoma.

Adolescent↗