Biomedical subjects

Y Okada

Publications and source records attributed to Y Okada.

At least 397 records · Page 22Linked to original sources

PubMed1999

Phosphorylation and/or presence of serine 37 in the movement protein of tomato mosaic tobamovirus is essential for intracellular localization and stability in vivo.

The P30 movement protein (MP) of tomato mosaic tobamovirus (ToMV) is synthesized in the early stages of infection and is phosphorylated in vivo. Here, we determined that serine 37 and serine 238 in the ToMV MP are sites of phosphorylation. MP mutants in which serine was replaced by alanine at positions 37 and 238 (LQ37A238A) or at position 37 only (LQ37A) were not phosphorylated, and mutant viruses did not infect tobacco or tomato plants. By contrast, mutation of serine 238 to alanine did not affect the infectivity of the virus (LQ238A). To investigate the subcellular localization of mutant MPs, we constructed viruses that expressed each mutant MP fused with the green fluorescent protein (GFP) of Aequorea victoria. Wild-type and mutant LQ238A MP fusion proteins showed distinct temporally regulated patterns of MP-GFP localization in protoplasts and formation of fluorescent ring-shaped infection sites on Nicotiana benthamiana. However mutant virus LQ37A MP-GFP did not show a distinct pattern of localization or formation of fluorescent rings. Pulse-chase experiments revealed that MP produced by mutant virus LQ37A was less stable than wild-type and LQ238A MPs. MP which contained threonine at position 37 was phosphorylated, but the stability of the MP in vivo was very low. These studies suggest that the presence of serine at position 37 or phosphorylation of serine 37 is essential for intracellular localization and stability of the MP, which is necessary for the protein to function.

Alanine↗

PubMed1999

Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers.

BACKGROUND/AIM: Matrilysin is one of the matrix metalloproteinases that has a critical role in tumour invasion, and is often expressed in gastrointestinal cancers. The aim of this study was to examine the role of matrilysin in metastasis of human colorectal cancers. PATIENTS (SUBJECTS)/METHODS: The relation between matrilysin expression and Dukes's type was investigated immunohistochemically in 83 surgically resected colorectal cancers, including five with liver metastasis. Moreover, the effects of matrilysin on the in vivo invasive and metastatic potential of colon cancer cells transfected with matrilysin cDNA were examined after subcutaneous injection into SCID mice. RESULTS: In 46% of primary and all of metastatic liver tumours, over 10% of cancer cells were stained positively for matrilysin. The expression of matrilysin correlated significantly with the presence of nodal or distant metastases (p<0.05). In addition, matrilysin transfectants formed invasive tumours and multiple liver metastases in SCID mice, without producing any significant difference in the subcutaneous tumour growth from mock transfectants. Casein zymography showed that the invading and metastasised tumours showed conspicuous matrilysin activity, which correlated with the number of metastatic lesions (p<0.001). CONCLUSIONS: Matrilysin showed a correlation with metastasis in a cohort of 83 colorectal cancer patients and marked metastatic potentiation in human colorectal cancer xenografts, indicating that it may play a critical role in the metastatic pathway of colorectal cancers.

Animals↗

PubMed1999

Increase of the cellular growth of old human diploid fibroblasts by radical scavenger: water-soluble protein from broad beans.

There is increasing evidence that free radical scavengers play an important role in the aging process and the control of cellular growth. We purified a free radical scavenging protein, the water-soluble protein (WSP) from broad beans (Vicia faba). In this study, we examined the effect of WSP on cellular growth and in vitro life span in old human fetal lung fibroblasts (WI-38 and PDL 37-40, 78-84% of the maximum life span). Since WSP increased the cellular growth, we also examined the effect of WSP (1.25-5 microg/ml) on cytosolic antioxidant enzyme activities in the old cells treated or not with tert-butyl hydroperoxide (BHP) to elucidate the mechanisms of cell proliferation in the old cells. The cellular growth of old fibroblasts was greatly increased by WSP. In 1.25 and 2.5 microg/ml of WSP, the cell proliferation increased by 32 and 35%, respectively, as compared with controls. The maximum population doubling levels of the cells did not increase. In the cells incubated with BHP, the cytosolic superoxide dismutase activity was returned to its control value by WSP treatment (1.25-5 microg/ml). The cytosolic glutathione peroxidase activity progressively increased with increasing concentrations of WSP. On the other hand, the cytosolic superoxide dismutase activity after 1.25- and 2.5- microg/ml WSP treatment without BHP was increased by 189 and 144%, respectively. Similarly, the cytosolic glutathione peroxidase activity was increased by 67 and 53%, respectively. These results suggest that cytosolic antioxidant activities in old cells can be modulated by WSP treatment. We concluded that there was a correlation between the optimum WSP concentrations for the increase of cellular growth and the WSP concentrations required to exhibit these maximum enzyme activities.

Cell Division↗

PubMed1999

Inhibitory effect of chalcone derivatives on recombinant human aldose reductase.

More than fifty chalcone derivatives were synthesized to examine structure-activity relationships against human aldose reductase. Certain 2',4'-dihydroxychalcone derivatives inhibited human aldose reductase activities, and 2',4',2, 4-tetrahydroxychalcone and 2',4',2-trihydroxychalcone showed potent inhibitory activity with IC50 values of 7.4x10(-9) M and 1.6x10(-7) M, respectively. On the other hand, cis-form chalcones, which were isomerized from the original trans-forms by irradiation of daylight in methanol solution, promoted the activity of human aldose reductase.

Aldehyde Reductase↗

PubMed1999

Amino acids and peptides. LIV. Application of 2-adamantyl derivatives as protecting groups to the synthesis of peptide fragments related to Sulfolobus solifataricus ribonuclease. I.

The 2-adamantyloxycarbonyl group was employed for the protection of the epsilon-amino group of Lys and the hydroxyl group of Tyr, and the 2-adamantyl ester was employed for the protection of the beta-carboxyl group of Asp in order to construct eight peptide segments as building blocks for the preparation of peptide fragments related to the sequence of Sulfolobus solifataricus Ribonuclease. The usefulness of the above protecting groups developed in our laboratory was confirmed.

Adamantane↗

PubMed1999

Amino acids and peptides. LV. Application of 2-adamantyl derivatives as protecting groups to the synthesis of peptide fragments related to Sulfolobus solifataricus ribonuclease. II.

Segment condensations were performed to construct peptide fragments related to Sulfolobus solifataricus Ribonuclease. At each condensation step, the new protecting groups were stable. The protected peptide fragments were treated with a low-high HF procedure to give the desired peptide fragments. These peptide fragments were also prepared by the solid-phase method, and the obtained peptides were compared with those obtained by the solution method. The peptide fragments obtained by the solution method were identical with those obtained by the solid-phase method on analytical HPLC, indicating that the new protecting groups could be easily removed by HF, and no racemization occurred during the synthesis of the protected peptides.

Adamantane↗

PubMed1999

Amino acids and peptides. LIII. Synthesis and biological activities of some pseudo-peptide analogs of PKSI-527, a plasma kallikrein selective inhibitor: the importance of the peptide backbone.

Pseudo-peptide analogs of trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-4-aminopheny l acetic acid (PKSI-527, plasma kallikrein selective inhibitor), in which an amide bond (peptide bond) has been replaced by a CH2-NH bond, i.e., trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (I), trans-4-aminomethylcyclohexanecarbonyl-psi (CH2-NH)-L-phenylalanyl-4-aminophenyl acetic acid (II) and trans-4-aminomethylcyclohexanecarbonyl-D-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (III) were synthesized. These pseudo-peptide analogs did not exhibit any detectable inhibitory activity against plasma kallikrein (PK), plasmin (PL), urokinase (UK), thrombine (TH) or trypsin (TRY). These results indicate that both carbonyl groups in the PKSI-527 are important for the manifestation of potent inhibitory activity against plasma kallikrein.

Animals↗

PubMed1999

Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor-binding activity.

Cyclization of dipeptidyl chloromethyl ketones gave 6-(4-aminobutyl)-3-carboxyethyl-5-methyl-2(1H)-pyrazinone, 3-(4-aminobutyl)-6-carboxyethyl-5-methyl-2(1H)-pyrazinone, and 3,6-bis(4-aminobutyl)-5-methyl-2(1H)-pyrazinone, which were inserted into the enkephalin sequence to give opioid mimetics. Thus, it was confirmed that a pyrazinone ring can be easily inserted into a peptide sequence in order to evaluate structural components required for biologically active peptides.

Chromatography, High Pressure Liquid↗

PubMed1999

Properties and the inclusion behavior of 6-O-alpha-D-galactosyl- and 6-O-alpha-D-mannosyl-cyclodextrins.

The novel heterogeneous branched cyclodextrins (CDs), 6-O-alpha-D- galactosyl-alpha, -beta, and -gamma CDs (Gal-alpha, -beta, and -gamma CDs) and 6-O-alpha-D-mannosyl-alpha, -beta, and -gamma CDs (Man-alpha, -beta, and -gamma CDs) dissolved sufficiently in water and in 10-50% (v/v) methanol aqueous solutions, as did the homogeneous branched CDs, 6-O-alpha-D-glucosyl-alpha, -beta, and -gamma CDs (Glc-alpha, -beta, and -gamma CDs). The solubilities of heterogeneous branched CDs were higher than those of each parent non-branched CDs. The hemolytic activities of heterogeneous and homogeneous branched CDs were lower than those of each parent non-branched CDs and the hemolytic activity became weaker in the order of non-branched CD > Man-CD > Glc-CD > Gal-CD in each series of alpha, beta, and gamma CD. AL type solubility-phase diagrams were displayed in the formation of inclusion complexes of the guest compounds of small size (methyl benzoate, estriol, and dexamethasone) with Gal-, Man-, and Glc-CDs, and marked differences among the three kinds of branched CDs could not be detected. However, solubility-phase diagrams between these branched CDs and the insoluble guest compounds of large cyclic structure (cyclosporin A, tacrolimus, and amphotericin B) showed AP type, and the improvement of water solubilities of these guest compounds with three kinds of branched CDs was enhanced in the order of Man-CDs > Glc-CDs > Gal-CDs.

Carbohydrate Conformation↗

PubMed1999

Synthesis of some pseudo-peptide analogs of thiol proteinase inhibitors.

Some pseudo-peptide analogs of thiol proteinase inhibitors were synthesized by a conventional solution method. Among them, Suc-Ala-Val-Val-Ala-psi-(CH2-NH)-Ala-pNA (peptide 1) and Suc-Ala-Val-Val-psi-(CH2-NH)-Ala-Ala-pNA (peptide 2) showed a stronger inhibitory activity compared with parent peptide such as Suc-Ala-Val-Val-Ala-Ala-pNA. In particular, peptide 2 was about 10-fold as active as the parent peptide (IC50 = 8 microM). Inserting psi-(CH2-NH) possibly makes the inhibitor less susceptible to papain and, as a result, produces more potent inhibition.

Buffers↗

PubMed1999

Complete atrioventricular septal defect associated with tetralogy of fallot: surgical indications and results.

Complete atrioventricular septal defect (AVSD) associated with tetralogy of Fallot is a rare condition that still has problems in the postoperative period. The authors report their surgical experiences over the past 10 years. Nine children underwent total correction. The defect was repaired by the 2-patch technique and the ATrioventricular valve was reconstructed by suturing the cleft and annuloplasty. A transannular right ventricular outflow patch was used in 5 patients. All patients had Down syndrome and a free-floating superior bridging lEAflet. One patient died from cardiac failure. Although there was no reoperation or death in the late postoperative periods, mild mitral regurgitation occurred in 4 patients and there was moderate or severe pulmonary regurgitation in 2 patients. All survivors currently have no critical symptoms in their daily lives. With the standard of patient selection used, the optimal body weight was around 8 kg and PA index was 200 or more. Right ventriculotomy provided a better view for complete closure of the ventricular septal defect (VSD). In order to avoid re-regurgitation of the atrioventricular valve, the 2-patch technique is the most suitable procedure for total repair.

Aortic Valve Insufficiency↗

PubMed1999

Noncardiogenic pulmonary edema as the chief manifestation of a pheochromocytoma: a case report of MEN 2A with pedigree analysis of the RET proto-oncogene.

Pheochromocytomas are rare neoplasias of the adrenal medulla which generally present with paroxysmal or sustained hypertension. Cardiogenic pulmonary edema is a common feature of these tumors, but few cases have been described with noncardiogenic pulmonary edema. We report a pheochromocytoma with the principle manifestation of noncardiogenic pulmonary edema and characterize a genetic lesion associated with the disorder. A 30-year-old man was admitted with abdominal pain and breathlessness. x-Ray examination of the chest revealed a massive, diffuse infiltration of the left lung without cardiomegaly. No paroxysmal blood pressure fluctuations or heart failure were evident during the entire course, and the infiltrate and dyspnea resolved in three days without inotropic or diuretic agents. Serum norepinephrine and epinephrine levels were elevated twenty and fifty times above normal, respectively. The patient was ultimately diagnosed with multiple endocrine neoplasia type 2A (MEN 2A). Mutations in the RET proto-oncogene have been described recently in patients with MEN 2A. Mutation analysis of selected RET exonic sequences identified a germline mutation at codon 634 in exon 11 of the RET proto-oncogene. The mutation introduces a transition encoding a non-conservative substitution from TGC (Cys) to CGC (Arg) and creates a novel restriction site recognized by HhaI. We further screened for this mutation among four of the proband's relatives by HhaI restriction analysis. One asymptomatic family member was identified who subsequently elected prophylactic total thyroid removal. Histological examination of this specimen confirmed the presence of medullary thyroid carcinoma.

Adrenal Gland Neoplasms↗

PubMed1999

Alpha-adrenergic blockade in preventing posttransplant edema of lung allograft.

Effect of alpha-adrenergic blockers on pulmonary edema in lung transplantation was studied with a rat model of syngeneic left lung transplantation. Prior to harvesting, 0.1 mg of Prazosin or 0.4 mg of Yohimbine was given to the donor. Pulmonary and systemic hemodynamics were measured under the right pulmonary arterial occlusion (RPAO) at different time points after grafting. Wet to dry weight ratio (W/D) of all transplants was also calculated. Same procedure was conducted in rats with normal and ischemic lung and in transplanted animals without any treatments. While RPAO did not increase W/D in normal lung with a significant elevation in pulmonary arterial pressure (PAP), both these values significantly increased in transplanted lung. Transplanted animals could not tolerate RPAO 24 hours after grafting, but were tolerable later than 48 hours with elevated W/D and PAP. On the contrary, animals given Prazosin or Yohimbine were all tolerable at 24 hours postsurgery. Yohimbine significantly improved W/D. Consequently, it was demonstrated that pulmonary edema of the graft reached its peak during first 24 to 48 hours after transplantation and was alleviated by the blockade of alpha-adrenergic receptor in the graft vessel.

Adrenergic alpha-Antagonists↗

PubMed1999

Mucosa-associated lymphoid tissue type lymphoma of the gallbladder associated with acute myeloid leukemia.

We describe a patient with mucosa-associated lymphoid tissue (MALT) type lymphoma of the gallbladder who developed concurrent acute myeloid leukemia (M2). She was admitted because of progressive jaundice and underwent cholecystectomy. Histologic examination of the gallbladder showed diffuse proliferation of atypical lymphoid cells and a formed lymphoepithelial lesion. Because of progressive thrombocytopenia, a bone marrow tap was performed 25 days after the operation. Bone marrow contained 65.5% blasts, and was positive for peroxidase, CD33 and HLA-DR, and negative for lymphoid markers. We discuss the rare association of these disorders.

Acute Disease↗

PubMed1999

Hemolytic uremic syndrome associated with immunoglobulin A nephropathy: a case report and review of cases of hemolytic uremic syndrome with glomerular disease.

A 35-year-old man with immunoglobulin A (IgA) nephropathy who developed hemolytic uremic syndrome (HUS) presented with transient elevation of serum creatinine, thrombocytopenia, and hemolytic anemia with fragmented red cells with nephrotic syndrome. Hemolytic anemia and the temporarily deteriorated renal function were improved after hemodialysis and plasma exchange. Histological findings were consistent with HUS and IgA nephropathy. Including this case, we reviewed the cases of HUS accompanied by glomerular diseases reported from 1969 to 1996. Surprisingly, most cases showed nephrotic syndrome at the onset of HUS. Several possible relationships between HUS and nephrotic syndrome are discussed.

Adult↗

PubMed1999

Persistent primitive hypoglossal artery associated with cerebral aneurysm and cervical internal carotid artery stenosis--case report.

A 71-year-old female had vertigo attacks once or twice a day secondary to vertebrobasilar insufficiency. Left carotid angiography revealed persistent primitive hypoglossal artery (PPHA) associated with a large internal carotid artery (ICA) aneurysm and severe stenosis of the ICA. The bilateral vertebral arteries were hypoplastic. The basilar artery was opacified via the PPHA but not via vertebral arteries. Clipping of the aneurysm was performed first because the risk of rupture of the aneurysm was not negligible. One month after clipping, carotid endarterectomy using a T-shaped shunt system was successfully performed. The postoperative course was uneventful and the vertebrobasilar ischemic attacks did not recur. Left carotid angiography demonstrated complete obliteration of the aneurysm and disappearance of the carotid artery stenosis. Low ICA flow (70 ml/min) and low stump pressure of the PPHA (25 mmHg) strongly suggested low perfusion of the posterior circulation. Carotid endarterectomy may be essential for augmentation of the posterior circulation in patients with PPHA associated with ICA stenosis.

Aged↗

PubMed1999

Cylindrical or T-shaped silicone rubber stents for microanastomosis--technical note.

The ostium of the recipient artery and the orifice of the donor artery must be clearly visualized for the establishment of microvascular anastomosis. Specially designed colored flexible cylindrical or T-shaped silicone rubber stents were made in various sizes (400 or 500 microns diameter and 5 mm length) and applied to bypass surgery in patients with occlusive cerebrovascular disease such as moyamoya disease and internal carotid artery occlusion. The colored flexible stents facilitated confirmation of the ostium of the artery even in patients with moyamoya disease and allowed precise microvascular anastomosis without problems caused by the stent.

Anastomosis, Surgical↗

PubMed1999

Neuroimaging findings of the development and resolution of solitary brainstem abscess: characteristics of neuroimagings in the early stage of brainstem abscess and importance of surgical management for brainstem abscess--case report.

A 64-year-old female presented with a solitary brainstem abscess. Magnetic resonance imaging and computed tomography demonstrated the development and resolution of the brainstem abscess with an unusual and fluctuating clinical course over several months. Serial neuroimaging examinations are required to detect a brainstem abscess in the early stage to establish the optimum treatment.

Brain Abscess↗