Biomedical subjects

Yuko Yamada

Publications and source records attributed to Yuko Yamada.

16 recordsLinked to original sources

PubMed2005

The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas.

Basal deposits within Bruch's membrane are associated with aging and age-related macular degeneration (AMD) although the factors causing their formation are incompletely understood. Advanced glycation endproducts (AGEs) accumulate in Bruch's membrane including basal deposits and drusen with aging. One mechanism by which AGEs alter a cell's phenotype is via AGE receptors. The purpose of this study was to immunolocalize and quantify the expression of AGE receptors by RPE cells associated with basal deposits or normal Bruch's membrane that were microdissected from human maculas. Postmortem eyes from 14 aged control donors and five donors with non-neovascular AMD were cryopreserved. RPE cells associated with normal Bruch's membrane or basal deposits were laser capture microdissected. The RNA was extracted and used for RT-qPCR to quantify the expression of RAGE, AGE R1, AGE R2, and AGE R3. Streptavidin alkaline phosphatase immunohistochemistry for these receptors was also performed and sections were bleached from 14 normal and nine AMD donors. RT-qPCR showed significant upregulation of RAGE, AGE R1, and AGE R3 in RPE cells overlying basal deposits compared to cells attached to morphologically normal Bruch's membrane. Immunohistochemical analysis for RAGE, AGER1, R2, and R3 showed diffuse, light staining of RPE cells and strong choriocapillaris staining in areas of normal Bruch's membrane. In areas of basal deposits, the RPE had more intense staining for RAGE and AGER1 compared to regions of normal Bruch's membrane. These results suggest that AGE receptors could influence the formation of basal deposits during aging and AMD.

Adult↗

PubMed2005

Bacillus subtilis tRNA(Pro) with the anticodon mo5UGG can recognize the codon CCC.

In Bacillus subtilis, four codons, CCU, CCC, CCA, and CCG, are used for proline. There exists, however, only one proline-specific tRNA having the anticodon mo(5)UGG. Here, we found that this tRNA(Pro)(mo(5)UGG) can read not only the codons CCA, CCG and CCU but also CCC, using an in vitro assay system. This means that the first nucleoside of its anticodon, 5-methoxyuridine (mo(5)U), recognizes A, G, U and C. On the other hand, it was reported that mo(5)U at the first position of the anticodon of tRNA(Val)(mo(5)UAC) can recognize A, G, and U but not C. A comparison of the structure of the anticodon stem and loop of tRNA(Pro)(mo(5)UGG) with those of other tRNAs containing mo(5)U at the first positions of the anticodons suggests that a modification of nucleoside 32 to pseudouridine (Psi) enables tRNA(Pro)(mo(5)UGG) to read the CCC codon.

Anticodon↗

PubMed2005

Long-term glial reactivity in rat retinas ipsilateral and contralateral to experimental glaucoma.

Although glaucoma is known to alter glial reactivity, the long-term effect of elevated intraocular pressure (IOP) on glial change has not been fully elucidated. This study aimed to examine how chronically elevated IOP induced by episcleral vein cauterization (EVC) in unilateral eyes affect reactivities of astrocytes and Müller cells of rats in the treated as well as contralateral eyes over time. EVC in unilateral eyes of Sprague-Dawley rats were performed to produce chronically elevated IOP. Flat mounted retina preparations were made at several points until 6 months, which were subjected to immunostaining for glial fibrillary acidic protein (GFAP). Retinal homogenates were one- or two-dimensionally electrophoresed, followed by GFAP immunoblotting. EVC significantly increased IOPs up to 27.8 from 13.1 mmHg, which gradually decreased over time. In flat mounted retinas, astrocytes lost but Müller cells gained GFAP immunoreactivity at 3 days after cauterization. The glial changes were partially reversed over time but last even after IOP normalization. In the contralateral eyes, similar glial changes gradually appeared at 1 month after EVC and thereafter. Immunoblotting demonstrated not only molecular size shifts but also alteration of isoelectric focusing of GFAP both in treated and contralateral retina as compared with age-matched control retina. EVC led to opposite reactions in astrocytes and Müller cells in terms of GFAP immunoreactivity. Late-onset glial reactivity also occurred in the contralateral retina.

Aging↗

PubMed2005

Multilineage involvement of light microscopic myeloperoxidase-negative acute leukemia.

The classification of acute leukemia has traditionally been based on a combination of morphology and cytochemical staining data, including myeloperoxidase (MPO) reaction; however, a recent World Health Organization (WHO) classification entails use of cytogenetic and molecular findings in addition to the classic morphological and immunophenotypic analyses. Nevertheless, there have been rare cases in which blastic cells show multilineage phenotypes. These cases may be classified as acute leukemia of ambiguous lineage in the recent WHO classification. We report the case of a 49-year-old man with acute leukemia with multilineage phenotypes. Morphological findings led to a diagnosis of acute myeloid leukemia M2 by the French-American-British classification, but at light microscopy the results of MPO staining were negative for blast cells. In contrast, results of reverse transcription polymerase chain reaction and fluorescence-activated cell sorter analyses were positive for expression of MPO messenger RNA and protein. The blast cells expressed CD4, CD19, CD22, CD33, CD38, CD79a, and HLA-DR and showed rearrangement of the immunoglobulin heavy chain and TCR-3 genes. Results of immunoelectron microscopic analysis of the blast cells were positive for MPO, CD19, CD33, CD34, CD38 and glycophorin A but not for platelet peroxidase. According to these results, the blast cells had at least 4 lineage phenotypes. We concluded that the multiparameter analyses conducted in this case, including immunological and ultrastructural assays, were important in arriving at the appropriate diagnosis of acute leukemia of ambiguous lineage in the new WHO classification.

Acute Disease↗

PubMed2004

Akt is activated via insulin/IGF-1 receptor in rat retina with episcleral vein cauterization.

The Akt serine/threonine kinase mediates pro-survival signalings in retina and was reported to be activated in a response to some retinal and optic nerve injuries. Human and experimental glaucoma induce apoptosis of retinal ganglion cells (RGCs). The purpose of this study is to test whether episcleral vein cauterization (EVC) to chronically elevate intraocular pressures (IOPs) in rats increase apoptosis of RGCs and affect activation of Akt and its upstream insulin-like growth factor (IGF)-1 receptor/Insulin receptor. Three episcleral veins in left eyes of Sprague-Dawley rats were cauterized to elevate IOPs. Up to 6 months, IOPs were monitored and the retina was dissected at several time points. The numbers of terminal dUTP nick end labeling (TUNEL)-positive cells and those of RGCs labeled with fluorogold were counted in flat-mounted retina. Immunohistochemistry and immunoblotting were performed to identify cells expressing phosphorylated Akt and to quantify the phospho- to total ratios of Akt and IGF-1 receptor/insulin receptor. EVC significantly elevated IOPs up to 2 months, increased TUNEL-positive cells in an IOP-dependent fashion, and reduced 34.5% of RGCs at 6 months (P<0.001) compared with contralateral retinas. Phosphorylated Akt was specifically expressed in RGCs until 1 month after cauterization. Akt (P=0.036) and IGF-1 receptor/Insulin receptor (P=0.003) were transiently phosphorylated at 3 days. Intrinsic activation of the IGF-1 receptor/Insulin receptor to Akt pathway may occur in RGCs in retina with EVC.

Animals↗

PubMed2004

Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs.

OBJECTIVES: To analyze retinal nerve fiber layer (RNFL) thickness in eyes with band atrophy by use of optical coherence tomography (OCT) and to evaluate the ability of OCT to detect this characteristic pattern of RNFL loss. DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: Thirty-four eyes of 18 patients with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors were studied. All eyes were divided into 3 groups according to visual field loss grading after Goldmann perimetry. INTERVENTIONS: Retinal nerve fiber layer thickness measurements with OCT. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness around the optic disc was measured by OCT (3.4-mm diameter circle). Calculation of the changes in OCT parameters, including the horizontal (nasal + temporal quadrant RNFL thickness) and vertical values (superior + inferior quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison between the 3 visual field grading groups was done with the analysis of variance test. The receiver operating characteristic (ROC) curve for the horizontal and vertical value were calculated, and the areas under the curve (AUC) were compared. RESULTS: Retinal nerve fiber layer thickness in eyes with band atrophy decreased in all OCT parameters. The reduction rate in average and temporal RNFL thickness and horizontal value was correlated with visual field grading. The AUC of horizontal value was 0.970+/-0.011, which was significantly different from AUC of vertical value (0.903+/-0.022). CONCLUSIONS: The degree of RNFL thickness reduction correlated with that of visual field defects. Optical coherence tomography was able to identify the characteristic pattern of RNFL loss in these eyes.

Area Under Curve↗

PubMed2004

Optimal designing of beta-conglycinin to genetically incorporate RPLKPW, a potent anti-hypertensive peptide.

Previously, we introduced the RPLKPW sequence, a highly potent hypotensive peptide designed based on ovokinin (2-7), into three homologous sites in the soybean beta-conglycinin alpha' subunit by site-directed mutagenesis. The modified protein expressed in Escherichia coli reduced blood pressure of spontaneously hypertensive rats (SHRs) after oral administration at a dose of 10 mg/kg, which suggested about 30% of the introduced peptide was released in vivo. In this study amino acid residues around the RPLKPW sequence were optimized with a use of synthetic peptides to facilitate release of RPLKPW by gastrointestinal proteases. Then, fourth RPLKPW was also introduced into the extension domain of the protein. The newly modified protein, which was produced in E. coli, significantly lowered blood pressure in SHRs at a dose of 2.5 mg/kg 4 h after oral administration. Furthermore, we produced an extension domain that corresponds to residues 1-143 of the modified alpha' subunit containing four RPLKPW sequences by introducing a termination codon. The minimum effective dose of the modified extension domain was 1.0 mg/kg, which is 1/2000 that of ovalbumin.

Administration, Oral↗

PubMed2004

[Analysis of retinal nerve fiber layer thickness measured by optical coherence tomography in glaucomatous eyes with hemifield defect].

PURPOSE: To analyze the retinal nerve fiber layer thickness(NFLT) as measured by optical coherence tomography(OCT) in glaucomatous eyes with hemifield defect and to evaluate the most effective parameter for the diagnosis of glaucoma with OCT. METHODS: One hundred eighty four(184) normal eyes(128 subjects) and 108 open-angle glaucomatous eyes(87 subjects) with superior or inferior hemifield defects verified by Humphrey field analyzer(HFA) were measured for NFLT with OCT. The correlations between NFLT and mean deviation on HFA were calculated. In combination with normal eye data, receiver operating characteristic curve(ROC curve) and AUC(area under the curve) of each NFLT in the affected hemifield were evaluated for the diagnosis of glaucoma. RESULTS: NFLT in both affected and unaffected hemifields was significantly correlated with mean deviation in HFA. An average of four 30 degrees segments close to the temporal side in the affected hemifield (parameter A120) had the highest correlation(r = 0.571) and the highest AUC(0.948) among all parameters. CONCLUSIONS: NFLT in the unaffected visual field decreases with the progression of glaucomatous damage. We suggest that the parameter A120 is the best indication in a diagnosis of glaucoma when measuring NFLT by OCT.

Adult↗

PubMed2003

Overexpression of receptor-type protein tyrosine phosphatase beta causes abnormal development of the cranial nerve in Xenopus embryos.

Roles of receptor-type protein tyrosine phosphatase beta (RPTPbeta, also called PTPzeta) were investigated in the nervous system development of Xenopus embryos. We previously showed that Xenopus embryos express mRNAs for 11 receptor-type (XRPTPbeta.1-XRPTPbeta.11) and two secretory (sXRPTPbeta.1 and sXRPTPbeta.2) variants generated by alternative RNA splicing. Whole-mount in situ hybridization analyzes demonstrated central nervous system-specific gene transcription in tailbud embryos. Distributions of mRNAs for receptor-type and secretory variants partially differ in the hindbrain. Overexpression of XRPTPbeta.4 or sXRPTPbeta.2, which was brought about by microinjection of the recombinant plasmid vectors, caused abnormal development of the cranial nerve X. Deletion of the cytoplasmic segment from XRPTPbeta.4 did not affect the ability to cause the abnormality, but deletion of the extracellular segment abolished it. These results suggest that normal development of the cranial nerve X requires regulated expression of the XRPTPbeta gene products.

Alternative Splicing↗

PubMed2003

tRNA1Ser(G34) with the anticodon GGA can recognize not only UCC and UCU codons but also UCA and UCG codons.

The tRNA1Ser (anticodon VGA, V=uridin-5-oxyacetic acid) is essential for translation of the UCA codon in Escherichia coli. Here, we studied the translational abilities of serine tRNA derivatives, which have different bases from wild type at the first positions of their anticodons, using synthetic mRNAs containing the UCN (N=A, G, C, or U) codon. The tRNA1Ser(G34) having the anticodon GGA was able to read not only UCC and UCU codons but also UCA and UCG codons. This means that the formation of G-A or G-G pair allowed at the wobble position and these base pairs are noncanonical. The translational efficiency of the tRNA1Ser(G34) for UCA or UCG codon depends on the 2'-O-methylation of the C32 (Cm). The 2'-O-methylation of C32 may give rise to the space necessary for G-A or G-G base pair formation between the first position of anticodon and the third position of codon.

Anticodon↗

PubMed2003

Design of a genetically modified soybean protein preventing hypertension based on an anti-hypertensive peptide derived from ovalbumin.

Food proteins can be a source of various bioactive peptides including such possessing anti-hypertensive activity. While most orally active anti-hypertensive peptides derived from food proteins inhibit the angiotensin I-converting enzyme (ACE), ovokinin (2-7) (RADHPF), a peptide isolated from a chymotryptic digest of ovalbumin, has been shown to induce nitric oxide-dependent vasorelaxation in an isolated mesenteric artery as well as anti-hypertensive effect after oral administration in spontaneously hypertensive rats (SHRs). Rational amino acid replacement lead to the ovokinin (2-7) analog, RPLKPW, which had the highest anti-hypertensive activity among the tested peptides. Furthermore, oral administration (0.1 mg/kg) of the peptide lowered the blood pressure of SHR but not of normotensive Wistar-Kyoto (WKY) rats. In order to develop a novel use of this potent anti-hypertensive peptide for prevention of hypertension, RPLKPW has been genetically introduced into the homologous sequences in soybean beta-conglycinin alpha' subunit by site-directed mutagenesis. The recombinant RPLKPW-incorporated alpha' subunit expressed in E. coil has been shown to exert anti-hypertensive activity after oral administration in SHR. Thus, RPLKPW-incorporated alpha' subunit is the first example of a genetically modified food protein possessing physiological activity based on a bioactive peptide.

Animals↗

PubMed2003

[The effect of corticosteroids on postoperative course after esophageal resection for carcinoma].

BACKGROUND: The effect of steroids against inflammatory mediators is well known, but its benefit and adverse effect on the postoperative clinical course are uncertain after esophageal resection for carcinoma. METHODS: Forty-three cases undergoing esophageal resection for carcinoma were studied retrospectively. Twenty-six cases, given corticosteroids during operation or first postoperative day, were classified as the steroid group, and the other 17 cases were defined as the control group. Postoperative courses, complications, and outcomes were compared between these 2 groups. RESULTS: In the steroid group, heart rate, body temperature and C-response protein were depressed during the postoperative period, and duration of systemic inflammatory response syndrome was 1.2 +/- 1.1 days compared with 2.7 +/- 1.4 days in the control group (P < 0.001). Although the duration of mechanical ventilation and ICU stay was unchanged, morbidity rate of postoperative anastomotic leakage was 15% in the steroid group compared with 47% in the control group (P < 0.05). The other morbidity rates of pulmonary complications, postoperative infection, arrhythmia, and liver dysfunction as well as mortality rate were similar between the 2 groups. CONCLUSIONS: Corticosteroids given in the early postoperative period depress systemic inflammatory response and attenuate the rate of postoperative anastomotic leakage after esophageal resection for carcinoma.

Adrenal Cortex Hormones↗

PubMed2003

[Changes in cytokines during perioperative period of hip arthroplasty in patients older than 80 years of age].

BACKGROUND: Elevations of plasma inflammatory cytokines are related to the surgical intervention. We have examined the circulating interleukin 6, 8 (IL-6, IL-8) and CRP responses in patients older than 80 years during orthopedic hip arthroplasty. METHODS: After taking the signed informed consent, 8 patients were enrolled in this study. All patients received standard spinal anesthesia combined with epidural catheterization. Samples were collected just before and after the surgery, and on 1st, 2nd and 7th day after the operation. RESULTS: Plasma IL-6 levels showed a significant increase on the day after surgery (5.6 +/- 3.7 vs. 52.2 +/- 24.1 pg.ml-1, mean +/- SD, P < 0.05), whereas although the levels of IL-8, increased (minimum 7.9 +/- 3.2 to maximum 70.3 +/- 80.2 pg.ml-1, mean +/- SD), the change was not significant. CRP levels were slightly elevated in the preoperative examination (2.8 +/- 3.5 mg.dl-1) and further increased on the 2nd day of surgery (8.3 +/- 5.4 mg.dl-1), but returned to a normal level on the 7th day. CONCLUSIONS: From the viewpoint of cytokines, this study showed that, although IL-8 level did not return to the preoperative value, the surgical stress of orthopedic hip arthroplasty in patients older than 80 years was almost of the same level as reported previously.

Aged↗

PubMed2002

Anesthetic management for a patient with Jansky-Bielschowsky disease.

PURPOSE: To describe the anesthetic management of a patient with Jansky-Bielschowsky disease (JBD), the late infantile form of neuronal ceroid lipofuscinosis, characterized by dementia, severe and drug resistant grand mal, myoclonic seizures, and blindness. CLINICAL FEATURES: A 14-yr-old girl with JBD was scheduled for resection of a gingival tumour and an infected sinus in the sacral area. Her preanesthetic examination revealed extreme muscle atrophy and dementia. Grand mal, myoclonic seizures, and upper airway obstruction were frequent. Following iv induction with thiamylal, anesthesia was maintained with sevoflurane, N(2)O and O(2). Her trachea was intubated without using muscle relaxants. Muscle relaxants were not used during the operation. Apart from an intractable hypothermia, the intraoperative course was uneventful. The emergence of anesthesia was smooth, except for persisting seizures. CONCLUSION: General anesthesia using thiamylal and sevoflurane provided satisfactory conditions during operation in a patient with JBD. Intraoperative hypothermia required particular attention.

Adolescent↗

PubMed2002

Design of a highly potent anti-hypertensive peptide based on ovokinin(2-7).

Ovokinin(2-7) (RADHPF), an orally active antihypertensive peptide derived from ovalbumin, lowers blood pressure in SHRs at a dose of 10 mg/kg. Attempts were made to potentiate its anti-hypertensive activity by replacing the amino acid residues in [Pro2, Phe3]-ovokinin(2-7), which was previously reported to have 33-fold stronger activity than ovokinin(2-7). The anti-hypertensive activity of [Pro2, Phe3]-ovokinin(2-7) was improved by replacement of the C-terminal Phe residue with Trp. Then, the best amino acid residues at other positions for the anti-hypertensive effect were selected. RPLKPW, the most potent derivative obtained, showed significant anti-hypertensive activities at a dose of 0.1 mg/kg after oral administration in spontaneously hypertensive rats (SHRs). Thus, RPLKPW showed 100-fold more potent anti-hypertensive activity than ovokinin(2-7).

Administration, Oral↗

PubMed2002

Effects of stereochemistry of sugars on protein stabilities.

We investigated thermal stabilities of four proteins in the presence of four kinds of sugars to analyze the mechanism of stabilization of proteins by additives. These proteins were stabilized by the addition of sugars, and the degree of stabilization correlated to the partial molar isentropic compressibility of the sugar.

Carbohydrate Conformation↗