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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 163 records · Page 9Linked to original sources

[Laparoscopic surgery for gastric cancer: indications and limitations].

Gastric cancer has been successfully treated by both endoscopic and open surgery, while early-stage gastric cancer with some risk of lymph node metastasis is managed with laparoscopic surgery. The principle of treatment of gastric cancer is to perform a complete resection of the lesion with safe and appropriate procedures based on disease stage. Three types of laparoscopic surgery have been reported: laparoscopy-assisted distal gastrectomy (LADG); laparoscopic local resection with the use of aT-fastener; and intragastric mucosal resection. In local resection, there is a possibility that past of the lesion or lymph node metastases may remain. D2 lymph node dissection requires a longer operative time and technical difficulties causing postoperative complications may be encountered. At present, LADG is the preferred choice of treatment in patients with early-stage gastric cancers due to the acceptable length of surgery and simple lymph node harvesting. For the wider application of minimally invasive surgery, numerous advances in operative procedures, including hand-assisted surgery and sentinel node navigation surgery, are required, along with technical developments for more accurate diagnosis to offer ideal treatment for each stage of gastric cancer.

Adult↗

[Usefulness of CT-guided RFA for hepatocellular carcinoma].

US-guided puncture is the simplest and most popular method in the RFA treatment for HCC. However, depending on the location of tumors, it is often difficult to detect them by US. We report here the utility of CT-guided RFA for the treatment of HCC. We performed CT-guided RFA for 27 nodules in 21 patients with HCC from July 1999 to June, 2001. We used the LeVeen Needle Electrode made by Boston Company and the Cool-tip type electrode made by Radionics Company. We judged the effects of the treatment by dynamic CT within 7 days after RFA. We were able to accomplish the treatment for all patients with the exception of one case who developed severe pain during RFA. We experienced transient increases of AST/ALT in a few cases, subcutaneous emphysema in one case, pleural effusion and ascites in two cases, but conservative treatments were effective for all cases. US-guided puncture was especially useful for the treatment of the tumors localized below the diaphragm that were hardly detectable by US.

Aged↗

[The effect of halothane anesthesia on dopamine release induced by apomorphine or haloperidol--an in vivo microdialysis study in rats striatum].

Brain microdialysis was used to study in vivo releases and changes in dopamine (DA) concentration induced by neuroleptics in the rat striatum during halothane anesthesia. Rats were implanted with a microdialysis probe into the right striatum and allowed to move freely. After acquiring steady state of DA and metabolites concentrations, apomorphine 50 micrograms.kg-1 or haloperidol 200 micrograms.kg-1 was administered intraperitoneally with or without 1.5% halothane anesthesia for 1 h. Halothane anesthesia showed no effect on the decrease of DA induced by apomorphine, but halothane antagonized the increase of DA induced by haloperidol. Administration of haloperidol produced an increase in metabolites of DA and it was unchanged by halothane. Malignant syndrome is a well known complication caused by interaction of neuroleptics and anesthesia. The results of the present investigation suggest that the mechanism of malignant syndrome might be associated with the dopaminergic activity.

Anesthesia, Inhalation↗

[Assessment of myocardial fatty acid metabolism in patients with angina pectoris and diabetes mellitus using 123I-BMIPP myocardial scintigraphy].

PURPOSE: We studied the effect of myocardial ischemia and diabetes mellitus (DM) on the myocardial fatty acid metabolism using 123I-BMIPP myocardial scintigraphy. METHODS: We performed 123I-BMIPP myocardial scintigraphy in 50 patients with myocardial ischemia and without DM (AP), in 30 patients with myocardial ischemia and DM (AP + DM), 12 patients with DM and without myocardial ischemia (DM), and in 10 normal subjects (N). Myocardial uptake rate of 123I-BMIPP was obtained using the time activity curve. Myocardial washout rate of 123I-BMIPP was calculated using the polar images of early and delayed SPECT images. RESULTS: Myocardial uptake rate of 123I-BMIPP (%) were AP: 4.9 +/- 0.6, AP + DM: 5.5 +/- 0.5, DM 5.7 +/- 0.5 and N: 5.0 +/- 0.4. 123I-BMIPP myocardial uptake rate was increased in AP + DM and DM. 123I-BMIPP myocardial washout rate (%) were AP: 30.2 +/- 4.3, AP + DM: 24.5 +/- 3.9, DM: 16.1 +/- 2.8 and N: 19.4 +/- 3.2. 123I-BMIPP myocardial washout rate was increased in AP and AP + DM. 123I-BMIPP myocardial washout rate was increased particularly in patients with multi-vessels disease. 123I-BMIPP myocardial washout rate was decreased in DM. CONCLUSION: The present study suggested that diabetes mellitus increased myocardial fatty acid uptake and decreased myocardial fatty acid washout, and that myocardial ischemia increased myocardial fatty acid washout.

Aged↗

[Successful treatment of idiopathic pure red cell aplasia with antithymocyte globulin].

An 18-year-old woman was admitted to our hospital because of severe anemia on October 16, 1999. Laboratory data included hemoglobin 3.5 g/dl, reticulocytes 2,200/microliter, WBC 3,500/microliter, and Plt 38.5 x 10(4)/microliter. Bone marrow aspiration showed a normocellular marrow with severe erythroid hypoplasia, suggesting a diagnosis of pure red cell aplasia. Methylprednisolone pulse therapy was started on October 20, but there was no response. Administration of cyclosporine A (CyA; 400-450 mg) was begun on November 1, but again there was no response. Antithymocyte globulin (ATG; 800 mg/day for 5 days, 15 mg/kg) was started from December 1 in addition to prednisolone (60 mg/day) and CyA (450 mg/day). On day 7 of ATG therapy, the reticulocyte count began to increase, and reached a peak of 32.6 x 10(4)/microliter on day 20. The patient's hemoglobin level started to increase on day 13, and reached 8.5 g/dl on day 27. A complete response has been maintained up to the time of writing, and the hemoglobin level was 11.9 g/dl on December 14, 2000. This is the first detailed Japanese case report of successful treatment of pure red cell aplasia using ATG.

Adolescent↗

[A case of familial hypokalemic periodic paralysis with hyperuricemia during paralytic attack and genetic analysis of the pedigree].

We reported a 13-year-old boy and his family with hypokalemic periodic paralysis. He showed marked hyperuricemia during his paralytic attack, although neither ischemic forearm exercise test nor bicycle-ergometer exercise test revealed myogenic hyperuricemia when he was free from paralysis. Genetic analysis was performed to the proband and his affected elder brother, mother, and, maternal grand mother. We found the Arg528His mutation of CACNL1A3 gene in all the patients examined. The severity of the attacks and the age of onset did not vary in the different generations, and male predominancy was not evident in this family.

Adolescent↗

Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion.

Increased expression of matrix metalloproteinases (MMPs) has been associated with human glioblastoma tumor progression. In this study, we sought to down-regulate MMP-9 expression by stably transfecting a high-grade glioblastoma cell line with a plasmid vector capable of expressing an antisense transcript complementary to a 528-bp segment at the 5' end of human MMP-9 cDNA. Stable transfectants were obtained through selection with G418. Of the clones transfected with vector, sense, and antisense constructs, Northern blotting, Western blotting, and gelatin zymography showed that MMP-9 expression was significantly reduced only in the antisense-transfected cells. A Matrigel invasion assay revealed marked reductions in invasiveness for the antisense clones relative to the parental, vector, and sense clones. Cocultures of tumor spheroids and fetal rat brain aggregates showed that the antisense-transfected stable clones showed no invasion of the rat brain aggregates; in contrast, 90% of the parental, vector, and sense clones invaded the rat brain aggregates. Intracerebral injection of antisense stable transfectants in nude mice produced no tumors or very small tumors, but intracerebral injection of parental or vector clones did produce tumors. These results suggest that MMP-9 expression is essential for the invasiveness of glioblastoma cells.

Animals↗

Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type.

BACKGROUND: The most important parameters predicting outcome of patients with gastric carcinoma are the depth of wall invasion and the status of lymph node metastasis, but the prognostic significance of histologic type is unclear. The aim of this study was to clarify the prognostic value of two major histologic types of gastric carcinoma, that is well and poorly differentiated types. METHODS: Histopathologic findings and outcomes of 504 patients with gastric carcinoma were evaluated by well and poorly differentiated types. Well differentiated gastric carcinoma (WGC) included papillary and tubular adenocarcinomas, poorly differentiated medullary carcinoma, and well differentiated mucinous carcinoma; whereas poorly differentiated gastric carcinoma (PGC) included poorly differentiated scirrhous carcinoma, signet ring cell carcinoma, and poorly differentiated mucinous carcinoma. RESULTS: Patients with WGC were characterized by old age, male predominance, tumor location in the lower third of the stomach, small tumor size, and liver metastasis; whereas patients with PGC were distinguished by their tumor location in the middle third of the stomach, serosal invasion, lymph node metastasis, advanced stage, and peritoneal dissemination. The overall 5-year survival rate for patients with WGC was higher than that for patients with PGC (76% vs. 67%; P = 0.058), especially for patients with >/= 10 cm tumors (42% vs. 14%; P = 0.017). The 5-year survival rate for patients with serosa positive but node negative tumors was higher in WGC patients than in PGC patients (83% vs. 59%; P = 0.086); whereas the 5-year survival rate for patients with serosa negative but node positive tumors was lower in WGC patients than in PGC patients (63% vs. 88%; P = 0.008). Multivariate analysis indicated that among pathologic variables of the tumor, histologic type (WGC vs. PGC) was one of the independent prognostic factors. CONCLUSIONS: Histologic type is important for estimating the tumor progression and outcomes of patients with gastric carcinoma. In addition to the depth of wall invasion and status of lymph node metastasis, histologic type, including well or poorly differentiated type, should be evaluated in the management of gastric cancer.

Adenocarcinoma↗

Alternative splicing forms of the human CD1D gene in mononuclear cells.

CD1d is a critical molecule for the presentation of lipid antigens to natural killer (NK) T cells. To investigate the molecular complexity of CD1d, alternatively spliced transcripts in peripheral blood mononuclear cells from three healthy subjects were analyzed by PCR and sequencing methods. We found eight alternatively spliced variants of the CD1D gene (V1-V8), seven of which are newly established variants (V2-V8). V1 and V4 are in-frame; however, the other six variants (V2, V3, V5-V8) are out-of-frame. V1, V2, V4, and V5 lack a beta(2)-microglobulin binding site (alpha3 domain), indicating the unstable presentation of the CD1d molecule on the surface. In V2 and V5, the transmembrane region is absent, supporting a soluble CD1d. In the V3-V8 variants, the antigen binding region (alpha1 and alpha2 domains) is partially defective, suggesting incomplete functional products. In contrast, the V1 and V2 transcripts bear the complete antigen binding site, resulting in functional proteins. Especially, the V2 splicing variant might function as an inhibitory soluble CD1d molecule and regulate the presentation of antigens on APC to NKT cells.

Alternative Splicing↗

Initial Stage Dynamics of Bridging Flocculation of Polystyrene Latex Spheres with Polyethylene Oxide.

The kinetics of bridging flocculation of polystyrene latex (PSL) particles induced by addition of excess polyethylene oxide (PEO) in the initial stage was studied using standardized mixing flow generated in an end-over-end rotation apparatus. To clarify the effect of the rate of polymer supply, flocculation experiments were performed by changing polymer concentration (C(p)). As was found in previous investigation, the progress of flocculation is divided into two stages. The first stage is characterized by an enhancement of the rate of flocculation by polymer addition. The increase in polymer concentration results in a higher enhancement but in a shorter duration for this stage. In the second stage, the flocculation is essentially stopped due to the appearance of steric stabilization. It was found that the ultimate degree of flocculation goes through a maximum against C(p). That is, when C(p)>==1.0 ppm, the ultimate degree of flocculation decreases with increased C(p). In this region, a clear crossover from the first stage to the second stage was observed. In the extreme case, evidence of a slight setback of flocculation was confirmed, which implies the breakup of metastable bridges by the application of additional fluid shear. When C(p)<==1.0 ppm, the ultimate degree of flocculation decreases with decreased C(p). The crossover from the first stage to the second stage appears more gradual at lower C(p). These results were observed irrespective of ionic strength. This result was interpreted as the elimination of a bare surface due to the spreading of a steric layer of adsorbed polymer. The characteristic time for reconformation of the polymer at a bare colloidal surface was estimated to be a few seconds. Copyright 2000 Academic Press.

Journal Article↗

Midkine promoter-based adenoviral vector gene delivery for pediatric solid tumors.

It is important to develop a system to express therapeutic genes in tumor cells with sufficient selectivity for cancer gene therapy. Midkine (MK) is a newly identified heparin-binding growth factor that is transiently expressed in the early stages of retinoic acid-induced differentiation of embryonal carcinoma cells. It has been reported that many human malignant tumors express high levels of MK mRNA or protein. However, no MK expression is detected in human or mouse liver. These interesting features of MK led us to examine the MK promoter as a candidate for tumor-specific gene expression. We thus developed new recombinant adenoviral (Ad) vectors containing either luciferase reporter gene (AdMKLuc) or herpes simplex thymidine kinase gene (AdMKTK) under the control of the human MK promoter. AdMKLuc achieved relatively high activity in Wilms' tumor (G-401) and neuroblastoma (SK-N-SH) cell lines. In addition, AdMKTK induced marked cell death in response to ganciclovir (GCV) in these same lines. Conversely, very low activity of the MK promoter was observed in mouse liver in vivo compared with the cytomegalovirus promoter. Importantly, AdMKTK + GCV did not induce liver toxicity, whereas substantial toxicity was seen with AdCMVTK + GCV treatment. On the basis of these findings, we conclude that the MK promoter is a candidate tumor-specific promoter for Wilms' tumor or neuroblastoma.

Adenoviridae↗

Mechanisms of vasoinhibitory effect of cardioprotective agent, CP-060S, in rat aorta.

Vasoinhibitory effects of (-)-(S)-2-[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3, 4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thiazolidin- 4-one hydrogen fumarate (CP-060S), a synthesized cardioprotective agent, were examined. In the rat aortic rings, the contractile responses to cumulative application of angiotensin II, [Arg(8)]-vasopressin (vasopressin), or prostaglandin F(2alpha) were inhibited by CP-060S in a concentration-dependent manner. The Ca(2+)-induced contractions in the presence of vasopressin or prostaglandin F(2alpha) were also inhibited by CP-060S in a concentration-dependent manner. The inhibitory effect of 10(-5) M CP-060S on phenylephrine-induced contraction was as potent as that of 10(-6) M nifedipine, and the combined addition of 10(-6) M nifedipine and 10(-5) M CP-060S showed the effect similar to that of 10(-5) M CP-060S alone. In rat aorta loaded with a Ca(2+) indicator, fura-PE3, 10(-5) M CP-060S completely inhibited the high K(+)-induced increase in cytosolic Ca(2+) level ([Ca(2+)](i)) and contraction. In contrast, 10(-5) M CP-060S only partially inhibited the increase in [Ca(2+)](i) and contraction due to phenylephrine or prostaglandin F(2alpha). In the presence of 10(-6) M nifedipine, 10(-5) M CP-060S did not inhibit the increase in [Ca(2+)](i) and contraction induced by prostaglandin F(2alpha). In a Ca(2+)-free medium, the phasic increases in contraction and [Ca(2+)](i) induced by phenylephrine were not affected by 10(-5) M CP-060S. These results suggest that the vasoinhibitory effect of CP-060S in rat aortic rings is due mainly to the inhibition of L-type voltage-dependent Ca(2+)-channels.

Angiotensin II↗

Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by an intrahepatic inoculation with an expression plasmid.

We assessed the possibility of intrahepatic inoculation with a plasmid encoding hepatitis C virus (HCV) proteins to elicit HCV-specific cytotoxic T lymphocytes (CTL) in mice as a conventional animal model of HCV infection. BALB/c mice were intrahepatically or intramuscularly inoculated with an expression plasmid DNA encoding HCV structural proteins under the control of the elongation factor 1-alpha promoter. Expressions of HCV-core protein and envelope proteins (E1 and E2) in hepatocytes were detected immunohistochemically 6 days after inoculation. CTL responses were examined using target cells either pulsed with a specific peptide or infected with a recombinant vaccinia virus expressing HCV structural protein. Both intrahepatically and intramuscularly DNA-inoculated mice developed CD8(+), MHC class I-restricted CTL responses that recognized the peptide pulsed as well as HCV proteins expressing target cells. These studies demonstrated the usefulness of a murine model of HCV infection induced by direct intrahepatic DNA inoculation for understanding the immunopathogenic mechanisms in HCV infection.

Animals↗

Early and late recurrence after gastrectomy for gastric carcinoma. Univariate and multivariate analyses.

BACKGROUND: To the authors' knowledge, there are few studies regarding the predictors of early and late recurrence after gastrectomy for gastric carcinoma, and it is unknown whether prognostic factors can be applied to the timing of recurrence. The current study analyzed patients who died of recurrent gastric carcinoma and clarified histopathologic indicators associated with early and late recurrence. METHODS: The study included 138 patients who died of recurrent gastric carcinoma after gastrectomy that was performed in the Department of Surgery I, Oita Medical University, between 1982-1995. Clinicopathologic findings were compared between 104 patients who died within 2 years after gastrectomy (early recurrence group) and 34 patients who died > 2 years after gastrectomy (late recurrence group). Multivariate analysis was performed to determine the independent factors correlated with the timing of recurrence. RESULTS: When compared with the late recurrence group, the early recurrence group was characterized by a tumor size >/= 5 cm (92% in the early recurrence group vs. 74% in the late recurrence group), positive lymphatic invasion (64% vs. 38%), extended lymph node metastasis (73% vs. 35%), Stage III or IV disease (87% vs. 62%), and limited lymph node dissection (32% vs. 3%). The mean survival time was influenced by the lymphatic invasion (P < 0.01), vascular invasion (P < 0.05), level of lymph node metastasis (P < 0.01), stage of disease (P < 0.01), and extent of lymph node dissection (P < 0.01). On multivariate analysis, survival time was found to be associated independently with the stage of disease (Stage I, II vs. Stage III, IV) or the level of lymph node metastasis (N0, N1 vs. N2, N3). CONCLUSIONS: The stage of disease and level of lymph node metastasis were found to be the most significant factors independently associated with the survival time after gastrectomy for gastric carcinoma. Patients with more advanced stage of disease (Stage III, IV) or those with extended lymph node metastasis (N2, N3) frequently died of recurrence within 2 years after gastrectomy.

Aged↗

Morphological change, loss of deltapsi(m) and activation of caspases upon apoptosis of colorectal adenocarcinoma induced by 5-FU.

Apoptosis is clearly distinguished from necrosis, morphologically and chemically. Morphologically, apoptosis is characterized by a condensed nucleus and the disappearance of microvilli without disruption of the cytoplasm. In this report, we demonstrate that 5-fluorouracil (5-FU)-induced early apoptotic cells are characterized by (i) ultracondensed mitochondria, (ii) no change in the microvilli or nucleus, (iii) a high mitochondrial transmembrane potential (Deltapsi(m)), and (iv) being annexin V(negative). The early apoptotic cells also show the active forms of caspase 8 and caspase 9. They rapidly lose Deltapsi(m) after further incubation. Therefore, we conclude that the ultracondensation of mitochondria precedes the loss of Deltapsi(m) and the exposure of phosphatidylserine to the outer leaflet of the cell membrane.

Adenocarcinoma↗

Halothane anesthesia decreases the extracellular level of dopamine in rat striatum: a microdialysis study in vivo.

PURPOSE: In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. METHODS: Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. RESULTS: General anesthesia with halothane alone decreased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. CONCLUSION: These results suggest that halothane potently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum.

Journal Article↗

Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene with 5-fluorocytosine.

Transduction of the cytosine deaminase (CD) gene into tumor cells followed by administration of 5-fluorocytosine (5-FC), called 5-FC/CD gene therapy, was created as suicide gene therapy for various cancers. The uracil phosphoribosyltransferase (UPRT) gene, which is absent from mammalian cells, directly converts 5-fluorouracil (5-FU) to 5-fluorouridine 5'-monophosphate. We evaluated whether the coexpression of CD and UPRT genes could generate a synergistic antitumor effect on experimental brain tumors. In vitro study showed that 9L cells, transduced with the UPRT gene by an adenovirus, were 16 times more sensitive to 5-FU, and CD + UPRT-transduced cells were 6,000 times more sensitive to 5-FC than parent cells, indicating that the acquisition of CD and UPRT further increased the 5-FC sensitivity of 9L cells compared with cells transduced with CD alone. In a rat brain tumor model, decreased amounts of CD and UPRT vectors were inoculated into the tumors to detect any additional effect of UPRT. CD and UPRT coexpression followed by 5-FC administration showed an antitumor effect as detected by sequential magnetic resonance imaging. This therapy significantly prolonged animal survival. These results suggest that 5-FC/CD + UPRT gene therapy can enhance the antitumor effect of 5-FC/CD gene therapy. Consequently, this approach might be a more feasible modality for the treatment of malignant brain tumors.

Adenoviridae↗