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Biomedical subjects

Y Hatanaka

Publications and source records attributed to Y Hatanaka.

At least 19 recordsLinked to original sources
PubMed2007

Cotransduction of CCL27 gene can improve the efficacy and safety of IL-12 gene therapy for cancer.

Interleukin-12 (IL-12) is a potent antitumoral cytokine, but high doses are toxic. Herein, we demonstrate that combinational transduction of IL-12 and CC-chemokine ligand-27 (CCL27) genes into pre-existing murine OV-HM ovarian carcinoma and Meth-A fibrosarcoma, by using RGD fiber-mutant adenoviral vectors, could induce tumor regression and relieve systemic side effects more effectively than either treatment alone. The antitumor activity of the IL-12 and CCL27 combination treatment was T-cell-dependent, and development of long-term specific immunity was confirmed in rechallenge experiments. Immunohistochemical analysis of tumors transduced with CCL27 gene alone or cotransduced with IL-12 and CCL27 genes showed significant increases in numbers of infiltrating CD3(+) T cells, which included both CD4(+) and CD8(+) cells. Additionally, cotransduction with IL-12 and CCL27 genes could more efficiently activate tumor-infiltrating immune cells than transduction with CCL27 alone, as determined by the frequency of perforin-positive cells and expression levels of IFN-gamma. Furthermore, mice treated with the IL-12 and CCL27 combination compared with those treated with IL-12 alone showed milder pathological changes, for example, lymphocyte infiltration and extramedullary hematopoiesis, in lung, liver and spleen. Our data provide evidence that combinational in vivo transduction with IL-12 and CCL27 genes is a promising approach for the development of cancer immunogene therapy that can simultaneously recruit and activate tumor-infiltrating immune cells.

Adenocarcinoma↗
PubMed2006

Spread of the radial SNAP: a pitfall in the diagnosis of carpal tunnel syndrome using standard orthodromic sensory conduction study.

OBJECTIVE: To investigate the occurrence of the spread of the radial sensory nerve action potential (SNAP) among patients with carpal tunnel syndrome (CTS) during standard median orthodromic sensory conduction study (SCS) using index finger stimulation. METHODS: We prospectively examined 74 hands in 56 CTS patients. We stimulated the index finger using ring electrodes. SNAPs were recorded at wrist over median and radial nerves. RESULTS: A spread of radial SNAP was clearly identified over the median nerve despite its small amplitude, in 72/74 hands during stimulation of the base of the index finger. In hands with delayed median SNAP, two peaks were observed; however in hands with absence of genuine median SNAP, only one peak of the spread was noticed. The proximal interphalangeal joint (PIP) stimulation still elicited an identifiable spread in 47/74 hands. CONCLUSION: This spread phenomenon is a previously undescribed pitfall during the standard median orthodromic SCS, frequently occurring in CTS patients. SIGNIFICANCE: In severe CTS cases, one may make wrong conclusion of normal median sensory latency if unaware of this pitfall.

Action Potentials↗
PubMed2006

Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector.

Our goal in the present study was to evaluate antitumor effects and frequency of tumor-infiltrating immune cells upon intratumoral injection of RGD fiber-mutant adenoviral vector (AdRGD) encoding the chemokines CCL17, CCL19, CCL20, CCL21, CCL22, CCL27, XCL1, and CX3CL1. Among eight kinds of chemokine-expressing AdRGDs, AdRGD-CCL19 injection most efficiently induced infiltration of T cells into established B16BL6 tumor parenchyma, whereas most of these T cells were perforin-negative in immunohistochemical analysis. Additionally, the growth of AdRGD-CCL19-injected tumors decreased only slightly as well as that of other tumors treated with each chemokine-expressing AdRGD, which indicated that accumulation of naive T cells in tumor tissue does not effectively damage the tumor cells. Tumor-bearing mice, in which B16BL6-specific T cells were elicited by dendritic cell-based immunization, demonstrated that intratumoral injection of AdRGD-CCL17, -CCL22, or -CCL27 could considerably suppress tumor growth and attract activated T cells. On the other hand, AdRGD-CCL19-injection in the immunized mice showed slight increase of tumor-infiltrating T cells compared to treatment using control vector. Collectively, although AdRGD-mediated chemokine gene transduction into established tumors would be very useful for augmentation of tumor-infiltrating immune cells, a combinational treatment that can systemically induce tumor-specific effector T cells is necessary for satisfactory antitumor efficacy.

Adenoviridae↗
PubMed2005

Vasodilative effect of perillaldehyde on isolated rat aorta.

The vasodilative effect of perillaldehyde, one of the major oil components in Perilla frutescens BRITTON, was studied using isolated rat aorta. Perillaldehyde at final concentrations of 0.01 to 1 mM showed dose-dependent relaxation of the aorta contracted by treatment with prostaglandin F2alpha or norepinephrine. Neither the presence of NG-nitro-L-arginine methyl ester nor removal of the aortic endothelium affected the vasodilatation, suggesting that perillaldehyde exerts a direct effect on vascular smooth muscle cells. The vasodilative effect of perillaldehyde was not inhibited by pretreatment with a beta-adrenergic receptor blocker (propranolol), an inhibitor of phosphodiesterase (theophylline), a delayed rectifier K+ channel blocker (tetraethylammonium chloride), or an ATP-sensitive K+ channel blocker (glibenclamide). However, perillaldehyde showed contrasting effects on vasodilatation of the aorta contracted by an influx of extracellular Ca2+ - perillaldehyde caused little vasodilatation on the aorta contracted by the Ca2+ ionophore A23187, while it inhibited the vasoconstriction induced by treatment with high-concentration K+, which dominantly opened the voltage-dependent Ca2+ channel. These results suggest that the vasodilative effect of perillaldehyde is derived from blocking the Ca2+ channels.

Animals↗
PubMed2004

N10 component in median nerve somatosensory evoked potentials (SEPs) is not an antidromic motor potential.

OBJECTIVE: To test the hypothesis that the N10 far-field potential in median nerve somatosensory evoked potentials is generated by the motor axons by examining patients with amyotrophic lateral sclerosis (ALS). METHODS: Subjects were 5 ALS patients showing pronounced or complete denervation of median-innervated small hand muscles. We evaluated N10 over scalp, and proximal plexus volleys (PPVs) at lateral or anterior cervical electrode. RESULTS: N10 and PPVs were definitely preserved for every ALS subject. N10 amplitudes of ALS subjects were even significantly larger than control subjects. In one ALS patient completely lacking motor axons, N10 was larger than the largest one among control subjects. CONCLUSIONS: Present results clearly indicate that N10 is not predominantly generated by motor axons but by the whole median nerve dominated by sensory axons. We propose a theory that N10 is a junctional potential generated by the entrance of the median nerve into bone at the intervertebral foramen, producing a positive pole at the non-cephalic reference electrode. Significantly larger N10 in ALS subjects may be due to the lack of cancellation by slower motor axons. SIGNIFICANCE: The hypothesis that N10 is generated by motor axons is refuted, and a new theory of its generation is presented.

Aged↗
PubMed2003

Postrenal acute renal failure during pregnancy 20 years after antireflux surgery.

We report that a 27-year-old woman with bilateral severe hydronephorosis during pregnancy 20 years after antireflux surgery. The patient developed postrenal acute renal failure due to obstruction of the lower ureter. This patient could safely give birth after bilateral percutaneous nephrostomy through joint management with the obstetrics and gynecology staff. We describe that stenosis of the lower ureter is a late complication of antireflux surgery.

Acute Kidney Injury↗
PubMed2001

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induces caspase-dependent apoptosis in mononuclear cells.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the tryptophan pyrolysates, is a dietary carcinogen and is formed in cooked meat and fish in our daily diet. Trp-P-1 will affect the cells in the blood circulation system before it causes carcinogenicity in target organs such as the liver. In this study, the cytotoxicity of Trp-P-1 was investigated in mononuclear cells (MNCs) from blood. Trp-P-1 (10-15 microM) decreased cell viability and induced apoptosis characterized both by morphological changes and by DNA fragmentation 4 h after treatment. DNA fragmentation was also observed following treatment at 1 nM after 24 h in culture. This result suggested that apoptosis would occur in the body following unexpected intake of foods containing Trp-P-1. To determine the mechanism of apoptosis, we investigated the activation of the caspase cascade in MNCs. Trp-P-1 (10-15 microM) activated the caspase cascade, i.e. the activity of caspase-3, -6, -7, -8 and -9 increased dose-dependently using peptide substrates, the active forms of caspase-3, -8 and -9 were detected by immunoblotting, and cleavage of poly(ADP-ribose) polymerase and protein kinase C-delta as the intracellular substrates for caspases was observed. A peptide inhibitor of caspase-8 completely suppressed activation of all other caspases, while an inhibitor of caspase-9 did not. These results indicated that caspase-8 may act as an apical caspase in the Trp-P-1-activated cascade.

Acetylcysteine↗
PubMed2001

Synthesis of biotinylated bis(D-glucose) derivatives for glucose transporter photoaffinity labelling.

New diazirine based bis-glucose derivatives for tagging glucose transporters have been synthesised. These included two biotinylated compounds linked either by an aminocaproate or by a cleavable dithiol link. These compounds have been derivatised via a key skeleton compound that can be easily used for introduction of additional tags. Studies on the erythrocyte glucose transporter (GLUT1) and the insulin-stimulated adipose cell transporter (GLUT4) have revealed the biotinylated photoreactive bis-glucose compounds are effective labelling reagents.

Adipocytes↗
PubMed2001

A model of photoprobe docking with beta1,4-galactosyltransferase identifies a possible carboxylate involved in glycosylation steps.

A molecular docking study has been performed on the interaction of beta1,4-galactosyltransferase with an acceptor site photoprobe. This is based on an acceptor site peptide fragment which was recently identified by the use of a photoprobe. The present model strongly suggests that the carboxylate group of Asp318 could be involved in the activation of the acceptor sugar 4-OH for the efficient galactosyltransfer. The result also exemplified that the combination of photoaffinity labeling with crystallography is a powerful method for the detailed structural analysis of ligand protein complex.

Aspartic Acid↗
PubMed2001

Single fiber EMG and repetitive nerve stimulation of the same extensor digitorum communis muscle in myasthenia gravis.

OBJECTIVE: To compare voluntary single fiber electromyography (v-SFEMG) and repetitive nerve stimulation (RNS) at the same extensor digitorum communis (EDC) muscle in myasthenia gravis (MG). METHODS: We examined v-SFEMG and RNS successively on the same day in the same EDC muscle. We studied 45 examinations of both v-SFEMG and RNS in 29 patients suffering from MG, together with examinations of RNS in 30 control subjects. RESULTS: Forty-one of 45 (91%) v-SFEMGs showed abnormal results, whereas only 18/45 (40%) RNSs showed an abnormal decrement. The percentage of decrement showed similar correlations with 3 v-SFEMG parameters: percentage of abnormal pairs, percentage of blocking pairs, and the mean MCD value. Examinations showing a significant decrement in RNS had at least 60%, and usually no less than 90%, abnormal pairs, and 10-80% blocking pairs. Some muscles without a decrement had up to 50% blocking pairs. CONCLUSIONS: These results suggest that the blocking phenomenon observed in v-SFEMG is not a direct counterpart of the decrement in RNS. This must be partly because fibers contributing to the decrement are continuously blocked during voluntary contraction, and partly, because smaller motor units explored by v-SFEMG are probably more abnormal in MG than larger motor units mainly contributing to a decrement. Both factors make v-SFEMG much more sensitive than RNS.

Adult↗
PubMed2001

A common mutation of low-density lipoprotein receptor gene is associated with essential hypertension among Japanese.

Candidate genes offer one approach to the identification of the genetic susceptibility to hypertension. A common gene variant of the low-density lipoprotein (LDL) receptor gene (LDLR) that affects plasma LDL metabolism within the normolipidaemic range, may be such a candidate gene. A common mutation of LDLR, C1773T, was associated with lipid metabolism such that the T1773 allele increased plasma LDL levels in a Caucasian population. The present study examined whether C1773T/LDLR was associated with essential hypertension in a Japanese population. Subjects with essential hypertension (EHT, n = 300) with a family history of hypertension, and controls (NT, n = 310, sex- and age-matched with EHT) were recruited from among out-patients at Osaka University Hospital. A C1773T substitution at codon 570 in LDLR was determined using PCR-Hinc II-RFLP. It was revealed that the C1773 allele was significantly more frequent (0.89) among hypertensive patients (chi2 = 9.58, P < 0.01) than normotensives (0.83), the calculated odds ratio being 1.7 (95% CI: 1.2-2.4). The effect of the T1773 allele on increasing cholesterol was significant in normotensives without antihyperlipidaemic medication, but not in hypertensives. After adjustments of confounding factors, the estimated odds ratio for hypertension in the subjects with C1773 homozygote increased to 2.1 (95% CI: 1.3-3.5), suggesting that this polymorphism is an independent risk factor for hypertension. Our results show that the C1773 mutant of LDLR increases susceptibility to hypertension, but not via hypercholesterolaemia.

Asian People↗
PubMed2001

Quantitative immunohistochemical evaluation of HER2/neu expression with HercepTestTM in breast carcinoma by image analysis.

HercepTestTM (DAKO A/S, Glostrup, Denmark) is an immunohistochemical assay that detects HER2/neu gene products, and evaluates the overexpression status of the HER2/neu protein in determining eligibility for the Trastuzumab (HerceptinR, Genentech, San Francisco, CA, USA) therapy. However, practically, interobserver variability of the HER2/neu interpretation of the immunostained results has caused marked disagreement with regard to the intensity of tumor staining. In this study, we quantitated HER2/neu expression by image analysis, and applied this analyzing system to help to minimize interobserver variability of the interpretation of the HercepTestTM. All the immunostained results were scored semiquantitatively on a range of 0 to 3+ in accordance with the criteria described as per the manufacturer's instructions, and quantitatively evaluated using an image analyzing system with image processing software. Among the 92 cases, 15 were scored as 3+, six were 2+, and 32 were 1+ under intraobservers agreement. When the cases were quantitated, a high correlation was shown between the signal area extracted by image analysis and the corresponding score of staining intensity with the HercepTestTM. By converting the quantitatively extracted data into a scoring system based upon the criteria, the outcome demonstrated a strong concordance with the scoring data obtained from immunostaining. The results indicated that a quantitative scoring system performed by simple image analysis may provide to improve interobserver agreement of the interpretation of the HercepTest TM in clinical practice.

Adult↗
PubMed2001

Lower cervical origin of the P13-like potential in median SSEPS.

The authors studied the origin of the scalp P13-like potential in median somatosensory evoked potentials, which have been reported to be preserved in patients with cervicomedullary lesions or in brain death. There were five patients with high to middle cervical lesions (C2/3 or C3/4 level). Small P13-like potentials after P11 were identified for all patients with a noncephalic reference but not with an ear reference. Their onset latencies were slightly earlier than the expected latency of the true P13/14 onset. In two patients, delayed true P13/14s followed by N18s were identified with both noncephalic and ear references. The authors argue that the P13-like potential observed in these patients is a different entity from scalp P13 in normal subjects. Because the C3/4 vertebral level corresponds to the C5 cord level, the origin of the P13-like potential must be below C5, contradicting the previous opinion that it is generated at the cervicomedullary junction or at the high cervical dorsal column. The authors named this potential lower cervical P13 (or lcP13), and present an opinion that it is generated by the beginning of the second spinal ascending volley, which has been described by direct-recording studies in humans.

Adult↗
PubMed2001

Development of an automated method for detecting mammographic masses with a partial loss of region.

Recently, we have been developing several automated algorithms for detecting masses on mammograms. For our algorithm, we devised an adaptive thresholding technique for detecting masses, but our system failed to detect masses with a partial loss of region that were located on the edge of the film. This is a common issue in all of the algorithms developed so far by other groups. In order to deal with this problem, we propose a new method in the present study. The partial loss masses are identified by their similarity to a sector-form model in the template matching process. To calculate the similarity, four features are applied: 1) average pixel value; 2) standard deviation of pixel values; 3) standard correlation coefficient defined by the sector-form model; and 4) concentration feature determined from the density gradient. After employing the new method to 335 digitized mammograms, the detection sensitivity for the partial loss masses jumped from 70% to 90% when the number of false positives was kept constant (0.2/image). Moreover, a combination of the existing method and the new method improved the true-positive rate up to 97%. Such results indicate that the new technique may improve the performance of our computer-aided diagnosis system for mammographic masses effectively.

Algorithms↗
PubMed2001

Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats.

Dysregulations of apoptosis have been widely recognized as important events in multi-stage carcinogenesis. Bcl-x, a member of the Bcl-2 family, is known to act as a regulator of apoptosis. The present study was conducted to assess the role of altered Bcl-x protein expression in exogenous and endogenous hepatocarcinogenesis in rats. In the short-term exogenous models, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 200 mg / kg body weight, partially hepatectomized at the end of week 3, administered phenobarbital at a concentration of 0.05% from the end of week 2 for 6 weeks, and sacrificed. In the livers, glutathione S-transferase (GST-P)-positive, putative preneoplastic lesions were induced, and Bcl-x protein expression was decreased in 24.7% of such lesions. The incidence of GST-P-positive lesions with decreased Bcl-x increased depending on the size of the lesions; 18.9%, 32.4% and 86.5% in the lesions smaller than 0.03, between 0.03 and 0.3, and larger than 0.3 mm(2), respectively. In GST-P-positive lesions larger than 0.3 mm(2), both apoptosis induction and cell proliferation activity were enhanced when Bcl-x protein expression was decreased. In the long-term exogenous models, rats were given 10 mg / kg of DEN, partially hepatectomized 4 h after treatment, administered 0.5 mg / kg of colchicine at the end of days 1 and 3, subjected to a selection procedure, and sacrificed at the end of week 45. Hepatocellular carcinomas were induced with the decreased Bcl-x protein expression. In the endogenous model, rats were fed a choline-deficient, L-amino acid-defined diet for 16 or 80 weeks and sacrificed. Bcl-x protein expression was decreased both in GST-P-positive lesions and hepatocellular carcinoma. These results suggest that this decrease of Bcl-x protein might serve as an indicator of the advanced form of preneoplastic lesions, and that this decrease could also be associated with a potential to progress into carcinoma in both exogenous and endogenous hepatocarcinogenesis of rats.

Alkylating Agents↗
PubMed2001

Angiotensin-converting enzyme inhibition with enalapril slows progressive intima-media thickening of the common carotid artery in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND AND PURPOSE: Whether angiotensin-converting enzyme (ACE) inhibitors have any clinically significant antiatherogenic effects in humans remains unproven. We undertook a prospective randomized clinical trial of 98 patients with non-insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of ACE inhibition with enalapril for preventing intima-media (IM) thickening of the carotid wall as measured ultrasonographically. METHODS: Ninety-eight NIDDM patients were randomly assigned either to enalapril at 10 mg/d (n=48) or to a control group (n=50); the planned duration of the trial was 2 years. All patients were seen at baseline (study entry) and 2 subsequent formal annual evaluations, in addition to standard clinical management for NIDDM. IM thickening and vascular lumen diameters were determined for all patients on the basis of baseline and 2 subsequent annual evaluations with carotid ultrasonography. We performed an intent-to-treat analysis to assess changes in IM thickening over the course of the study. RESULTS: Annual IM thickening measurements of the right and left common carotid arteries were 0.01+/-0.02 and 0.01+/-0.02 mm/y in the enalapril-treated group and 0.02+/-0.03 and 0.02+/-0.02 mm/y in the control group, respectively (P<0.05). From regression analysis, annual IM thickening was found to be predicted by enalapril use, sex, and insulin use (F(3,94)=3.86, P=0.012). When we controlled for these other variables, enalapril use reduced annual IM thickening of right and left common carotid arteries by 0.01+/-0.004 mm/y relative to the control group over the course of this study. CONCLUSIONS: Long-term treatment with an ACE inhibitor (enalapril) slows progressive IM thickening of the common carotid artery in NIDDM patients.

Angiotensin-Converting Enzyme Inhibitors↗