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Y Kaneda

Publications and source records attributed to Y Kaneda.

At least 343 records · Page 19Linked to original sources
PubMed1995

Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat angiotensinogen.

The renin-angiotensin system plays an important role in blood pressure regulation. Angiotensinogen, which is mainly produced in the liver, is a unique component of the renin-angiotensin system, because angiotensinogen is only known as a substrate for angiotensin I generation. It is unclear whether circulating angiotensinogen is a rate-limiting step in blood pressure regulation. Recent findings of genetic studies and analyses suggest that the angiotensinogen gene may be a candidate as a determinant of hypertension. To test the hypothesis that angiotensinogen may modulate blood pressure, we transfected antisense oligonucleotides against rat angiotensinogen into the rat liver via the portal vein using liposomes that contain viral agglutinins to promote fusion with target cells, a technique that has been reported to be highly efficient. Transfection of antisense oligonucleotides resulted in a transient decrease in plasma angiotensinogen levels in spontaneously hypertensive rats from day 1 to day 7 after the injection, consistent with the reduction of hepatic angiotensinogen mRNA. Plasma angiotensin II concentration was also decreased in rats transfected with antisense oligonucleotides. Moreover, a transient decrease in blood pressure from day 1 to day 4 was observed, whereas transfection of sense and scrambled oligonucleotides did not result in any changes in plasma angiotensinogen level, blood pressure, or angiotensinogen mRNA level. Overall, our results demonstrate that transfection of antisense oligonucleotides against rat angiotensinogen resulted in a transient decrease in the high blood pressure of spontaneously hypertensive rats, accompanied by a decrease in angiotensinogen and angiotensin II levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

[Experience of absorbable staple in lobectomy].

We examined the differences between absorbable staple and un-absorbable staple in inflammatory reaction during the early post-operative period in lung cancer patients. From october 1993 to august 1994, absorbable staples (GIA 75-.060; United States Surgical Co., Ltd.) or un-absorbable staples (Multifire GIS 60 Titanium (3.8mm); United States Surgical Co., Ltd.) were applied in 10 lung cancer patients each. Duration of air leakage, massive pleural effuion (more than 100 ml/day), and high fever (over 38 degrees C), as well as the changes of leukocyte counts in peripheral venous blood and C reactive protein were compared between the two groups. The absorbable staple group show a mildly increased inflammatory reactions than those of un-absorbable staple group, but those were not significant differences. Absorbable staple was shown to be completely absorbed until 6 months in animal model. Absorbable staple is thought to be superior to un-absorbable staple, instead of mildly increased inflammatory reaction during the early post-operative period.

Absorption↗
PubMed1995

[Imaging diagnosis of Creutzfeldt-Jakob disease].

Creutzfeldt-Jakob disease (CJD) is one of the "prion" diseases. MRI has been reported to detect some findings in this disease, particularly high intensity in the basal ganglia on T2WI. We reviewed six cases of CJD, and found additional characteristic findings. Cerebral atrophy was detected in two of six cases, and in one of these two, it progressed markedly during 8 months. No abnormal density or abnormal signal intensity was detected on CT or T1WI of MRI. Cerebral angiography was done in one patient, and no abnormality was detected. High signal intensity on T2WI in the basal ganglia was detected in five of six cases (83%). T2WI showed high signal intensity in the cerebral cortex in four of six cases (67%), and in three cases the temporal cortex was involved. The high signal intensity in the temporal cortex appeared prior to the appearance of abnormal intensity in the basal ganglia in two cases. We conclude that the high signal intensity in the temporal cortex on T2WI is an important sign and can lead to early diagnosis of CJD. We consider that these MR findings may represent a "prion" disease, not only CJD.

Aged↗
PubMed1995

Synthetic cell-adhesive laminin peptide YIGSR conjugated with polyethylene glycol has improved antimetastatic activity due to a longer half-life in blood.

This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.

Animals↗
PubMed1995

Effect of angiotensinogen on blood pressure regulation in normotensive rats: application of a loss of function approach.

OBJECTIVE: To investigate the effect of plasma angiotensinogen on blood pressure regulation in normotensive rats, by a loss of function approach using antisense oligonucleotides. DESIGN AND METHODS: Eight-week-old male Wistar rats were transfected with antisense, sense or scrambled oligonucleotides using liposomes containing viral agglutinins, which are reported to be highly efficient in promoting fusion with target cells. The abdomen was opened with a median incision, and the liver and portal vein were exposed. Then 2.5 ml of hemagglutinating virus-liposome complex containing oligonucleotides was introduced into the liver by multiple direct injections or infusion via the portal vein. Blood pressure, plasma angiotensinogen and angiotensin II levels were measured after transfection. The hepatic angiotensinogen level was examined by Northern blotting and radioimmunoassay. RESULTS: The in vivo injection of antisense oligonucleotides against rat angiotensinogen by the hemagglutinating virus-liposome gene transfer method into normotensive rats resulted in a transient fall in blood pressure from day 1 to day 4 after injection. This was accompanied by a decrease in plasma angiotensinogen and hepatic angiotensinogen messenger RNA levels on day 2. No significant changes were noted in untreated rats or those treated with sense or scrambled oligonucleotides. Plasma angiotensin II concentration was also reduced by antisense treatment, but not sense or scrambled treatment. CONCLUSIONS: In vivo administration of antisense angiotensinogen oligonucleotides resulted in a transient decrease in blood pressure accompanied by a decrease in plasma angiotensinogen and angiotensin II levels, which suggests that angiotensinogen plays a pivotal role in the regulation of blood pressure in normotensive rats.

Angiotensin II↗
PubMed1994

Pharmacokinetics of antisense oligodeoxyribonucleotides (cyclin B1 and CDC 2 kinase) in the vessel wall in vivo: enhanced therapeutic utility for restenosis by HVJ-liposome delivery.

Using a highly efficient viral HVJ (hemagglutinating virus of Japan) liposome-mediated transfer method, we examined the cellular fate of antisense oligodeoxyribonucleotides (oligos) in the vessel wall in vivo. Direct transfer of unmodified FITC (fluorescein isothiocyanate)-labeled oligos into injured rat carotid arteries showed, localized in the medial layer, fluorescence that disappeared within 1 day. In contrast, transfection of unmodified FITC-oligos by the HVJ-liposome method showed, concentrated in the medial layer, high levels of fluorescence that were sustained for at least 1 week. Moreover, we demonstrated nuclear localization and accumulation of fluorescence in the vessel wall using this method. To examine the therapeutic utility of this method, we transferred antisense phosphorothioate oligos against cyclin B1- and CDC2 kinase-encoding genes into balloon-injured rat carotid artery as a potential therapy for experimental restenosis. Two weeks after transfection, antisense oligo treatment directed against either CDC2 kinase or cyclin B1 resulted in a partial, but significant, inhibition in neointima formation. In contrast, transfection of either sense or scrambled control oligos had no effect. Interestingly, co-transfection of antisense oligos against CDC2 kinase and cyclin B resulted in further inhibition of neointima formation, as compared to blockade of either gene target alone. These results demonstrate that: (i) the HVJ-liposome method enhances the half life and nuclear localization of antisense oligos in the vessel wall in vivo; and (ii) HVJ-mediated administration of antisense CDC2 kinase and cyclin B1 oligos produces a sustained inhibition of neointima formation after balloon angioplasty.

Animals↗
PubMed1994

Chromosomal pericentric inversion detected in a sow and her piglets.

Forty-four pigs with the suspicious symptoms of porcine stress syndrome (PSS) were selected for chromosome analysis. Cytogenetic evaluation by means of the G-banding technique revealed that one sow had an abnormal (38,XX, inv (1p+q-) (2.1;1.1) karyotype. The same abnormality was also detected in 8 of 13 offspring of this sow. However, there was no correlation between the chromosome abnormality and PSS. The chromosome abnormality did not give rise to a reduction in the fertility of this sow or in the viability of her offspring. This case represents the first reported instance of pericentric inversion in swine.

Journal Article↗
PubMed1994

Reproductive failure in mice chronically infected with Toxoplasma gondii.

Nya: NYLAR female mice infected with Toxoplasma gondii for 1 and 2 months were cohabited with normal males for 1 week, then sequestered individually to monitor their reproductive performance. Mice bred 1 month postinfection (p.i.) exhibited reproductive failure, with 1 of 16 females delivering 2 sickly pups; in others, interruption of pregnancy and fetal wastage occurred. Mice infected for 2 months were uniformly infertile. Vaginal lavage showed cessation of estrus cycling and constant diestrus cytology at as early as 1 month p.i. Histologic examination of the ovaries revealed impaired folliculogenesis and few corpora lutea, if any. Uterine atrophy was marked. Coronal sections of the cerebrum disclosed widespread vasculitis, focal disruptions of the ependymal cell layer lining the lateral and third ventricles, and periventricular edema. We suggest that the reproductive failure of the infected mice is due to an acquired hypogonadotropic hypogonadism secondary to hypothalamic dysfunction.

Adrenal Glands↗
PubMed1994

Homologous cysteine proteinase genes located on two different chromosomes from Trypanosoma rangeli.

DNA fragments were obtained by the polymerase chain reaction (PCR) using genomic DNA from T. rangeli as template and oligonucleotide primers encoding the active site amino acids of cysteine proteinase. After amplification by PCR, several DNA products were observed. These were purified and used as templates for a second round of PCR. This resulted in two DNA products of 475 and 498 bp. The 498 bp DNA (Tr-CP) contained both the sense and antisense primer sequences, and encoded a polypeptide having substantial homology with eukaryotic cysteine proteinases. The other product (Tr-DMR), which lacked the antisense primer sequence, encoded a polypeptide having homology with the DNA mismatch repair gene from Saccharomyces cerevisiae. The overall homology of the Tr-CP-encoded polypeptide to the cysteine proteinases from other trypanosome species was 69% identity (T. cruzi) and 73% identity (T. brucei), respectively. Northern blot analysis revealed that the Tr-CP gene was specifically expressed in T. rangeli as a 1.7 kb mRNA. A karyotype map of the chromosomes was also performed using pulsed-field gradient gel electrophoresis and Southern blot hybridization with these genes. T. rangeli has 14 chromosome bands ranging from 350 kb to 1.6 Mb, which were fewer in number and smaller in size compared with those from T. cruzi. The Tr-CP fragment and the Tr-DMR fragment hybridized with equal intensity on chromosome 1 (350 kb) and chromosome 2 (470 kb), respectively. These results suggest that non-pathogenic T. rangeli contains a conserved gene corresponding to the cysteine proteinase or a closely related enzyme, and that there is more than one copy of this gene, each found on different chromosomes.

Amino Acid Sequence↗
PubMed1994

Antimetastatic effects of synthetic peptides containing the core sequence of the type III connecting segment domain (IIICS) of fibronectin.

The antimetastatic activities of synthetic peptides corresponding to fragments of the adhesion-related molecules, such as fibronectin and laminin, were examined. We prepared three peptides derived from the type III connecting segment domain (IIICS) of fibronectin: Glu-Ile-Leu-Asp-Val (EILDV), Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (EILDVPST), Arg-Glu-Asp-Val (REDV), and a laminin-related peptide, Tyr-Ile-Gly-Ser-Arg (YIGSR). Each peptide inhibited the experimental tumor metastasis of B16-BL6 melanoma, while EILDV had the strongest effect. The peptides conjugated with poly(ethylene glycol) (PEG) were more effective than the unmodified peptides in molar ratio terms. A mixture composed of PEG hybrids with EILDV, REDV and YIGSR significantly inhibited tumor metastasis.

Amino Acid Sequence↗
PubMed1994

Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides.

The cell cycle regulatory enzyme, cdk (cyclin-dependent kinase) 2 kinase, is activated in the rat carotid artery after balloon angioplasty injury, and may mediate smooth muscle proliferation. To test the hypothesis that inhibition of the expression of this key enzyme can inhibit intimal hyperplasia, we studied the effect of antisense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2 kinase administered by intraluminal delivery using hemagglutinating virus of Japan (HVJ)-liposome-mediated transfer. The specificity of antisense cdk 2 ODN was confirmed by the observation that mRNA level of cdk 2 kinase in injured vessels was markedly diminished by the antisense ODN treatment. At 2 wk after transfection, antisense cdk 2 ODN treatment (15 microM) resulted in a significant inhibition (60%) in neointima formation, compared with sense ODN-treated and untreated vessels. Since we have previously observed that cell division cycle 2 kinase mRNA was also activated after vascular injury, we administered the combination of antisense cdc 2 and cdk 2 ODN in this study. Antisense cdc 2 ODN alone (15 microM) only reduced intimal formation by 40%. Combined antisense treatment resulted in near complete inhibition of neointima formation. To understand the mechanism of the sustained effect of a single antisense ODN administration, we examined kinetics of ODN in the vessel wall. Using phosphorothioate FITC-labeled ODN, we transfected carotid artery using the HVJ-liposome method. Fluorescence localized immediately to the medial layer, and persisted up to 2 wk after transfection. These results demonstrate that a single intraluminal administration of antisense ODN directed to cell cycle regulatory genes (e.g., cdk 2 kinase) using the HVJ method can result in a sustained inhibition of neointima formation after balloon angioplasty in rat carotid injury model.

Angioplasty, Balloon↗
PubMed1994

Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth.

In addition to the atria, recent evidence suggests that atrial natriuretic peptide (ANP) is also synthesized in other tissues. Of particular interest is the location of ANP mRNA in the vessel wall. We and others have shown that exogenously added ANP inhibited the growth of endothelial cells and vascular smooth muscle cells (VSMC) in culture. However, it is not known if the locally synthesized ANP would act similarly. Because cultured endothelial cells and VSMC have lost the ability to express the endogenous ANP gene, we have transfected cells in culture with an expression vector expressing rat ANP and have examined the effects on growth. Cultured endothelial cells transfected with an ANP expression vector synthesized and secreted high levels of ANP. These cells also showed significantly lower rates of DNA synthesis under basal and fibroblast growth factor (FGF)-stimulated conditions. Addition of conditioned medium from endothelial cells transfected with ANP vector to nontransfected endothelial cells resulted in the significant increase in cyclic GMP. Similarly, conditioned media collected from endothelial cells transfected with ANP vector also decreased DNA synthesis in VSMC. Coculture of ANP-transfected endothelial cells with quiescent VSMC showed that released ANP from endothelial cells inhibited DNA synthesis in VSMC. Finally, we examined the autocrine effect of direct transfection of ANP vector into VSMC. Transfection of the ANP vector decreased DNA synthesis in VSMC under basal and angiotensin II-stimulated conditions. Similarly, transfection of the ANP vector resulted in a decrease in the PDGF and serum (5%)-stimulated DNA synthesis of VSMC. These results demonstrate that endogenously produced ANP can exert autocrine and paracrine inhibitory effects on endothelial cell and VSMC growth. In vivo gene transfer of ANP may provide us with the opportunity of gene therapy for vascular diseases in which the abnormalities are vasoconstriction and pathological growth.

Animals↗
PubMed1994

Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme.

In vitro studies have demonstrated that angiotensin (Ang) II directly stimulates vascular smooth muscle cell (VSMC) growth. However, it is still unclear if Ang II exerts a direct effect on vascular hypertrophy in vivo independent of its effect on blood pressure. In vivo gene transfer provides the opportunity to assess the effects of increased activity of the vascular angiotensin system in the intact animal while avoiding an increase in circulating angiotensin or in blood pressure. Accordingly, we transfected the human angiotensin converting enzyme (ACE) vector into intact rat carotid arteries by the hemagglutinating virus of Japan-liposome method. 3 d after transfection, we detected increased ACE activity in the transfected artery. Immunohistochemistry localized immunoreactive ACE in the medial VSMC as well as in the intimal endothelial cells. The increase in vascular ACE activity was associated with a parallel increase in DNA synthesis as assessed by BrdU (bromo-deoxyuridine) index and vascular DNA content. This increase in DNA synthesis was abolished by the in vivo administration of an Ang II receptor-specific antagonist (DuP 753). Morphometry at 2 wk after transfection revealed an increase in the wall to lumen ratio of the ACE-transfected blood vessel as compared with control vector transfected vessels. This was accompanied by increases in protein and DNA contents without an increase in cell number. Local transfection of ACE vector did not result in systemic effects such as increased blood pressure, heart rate, or serum ACE activity. These morphological changes were abolished by the administration of the Ang II receptor antagonist. In this study, we used in vivo gene transfer to increase local expression of vascular angiotensin converting enzyme and provided proof that increased autocrine/paracrine angiotensin can directly cause vascular hypertrophy independent of systemic factors and hemodynamic effects. This approach has important potentials for defining the role of autocrine/paracrine substances in vascular biology and hypertension.

Angiotensin I↗
PubMed1994

[Cytogenetic subtyping of salivary gland pleomorphic adenoma and carcinoma in pleomorphic adenoma].

Current research on salivary gland pleomorphic adenoma is aimed at grouping the cases by cytogenetical aberrations into several subtypes. In this report, 21 cases of pleomorphic adenomas were analysed cytogenetically and divided into 4 subtypes following Bullediek's method; normal karyotype (6 cases), 8q12 rearrangement (8 cases), 12q13-15 rearrangement (5 cases) and other aberrations (2 cases). The average occurrence age of each group was examined. The 8q12 rearrangement group (37.2 y.o.) was younger than the normal karyotype (49.2 y.o.) and 12q13-15 rearrangement groups (52.4 y.o.). Histological subtyping based on Seifert's classification was made and its relationship with the above cytogenetic subtypes was studied. In the 8q12 rearrangement group, Seifert's type-1 was predominant (88%), while in the normal karyotype and 12r13-15 rearrangement groups, Seifert's type-2 was the most common (50% and 80% respectively). We also examined 2 cases of carcinoma in pleomorphic adenoma. Although both showed some cytogenetic abnormalities, no aberrations specific to pleomorphic adenoma (8q12 or 12q13-15 rearrangement) were found. This suggests that original adenomas of these carcinomas showed a normal karyotype or other types of aberrations.

Adenocarcinoma↗
PubMed1994

[Congenital esophago-bronchial fistula in adult--report of a case].

A 52-year-old man had been having cough on drinking water since 30 years. He coughed out blood 20 years ago. Chest roentgenogram showed the infiltrating shadow in the right lower lung field and the left hilum. Chest computed tomogram in the left atrium level showed fistulous communication between the bronchus and the esophagus and cavity lesion. Esophagogram showed fistulous communication between the bronchus (rt. B7) and the middle third of the esophagus. Bronchogram showed the stenotic lesion of the right B7a and B*. And abnormal bronchus was revealed and fistula was suspected. The orifice of the fistula was seen by esophageal endoscopy. Through the right posterolateral thoracotomy, fistelectomy and covering with pleural flap over the esophageal suturing site were performed. Histologic finding of the resected specimen revealed fistula's wall composing of smooth muscle lined with squamous cell layer. This case is categorized as Braimbridge type II. The postoperative course was uneventful and the patient is now in free of complaints at the 6th month's P.O.D.

Bronchial Fistula↗