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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 55 records · Page 3Linked to original sources

Beneficial effects of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation using right lobe graft.

BACKGROUND: Recently, virtual operation planning and navigation systems have been introduced in the field of neurosurgery and orthopedic surgery. We report here the beneficial effects of 3-dimensional (3D) visualization on hepatic venous reconstruction in living donor liver transplantation (LDLT) using right lobe graft. METHODS: 3D-image reconstruction of the liver was rendered with 3-mm slices of helical computed tomography (CT) data using zioM900 (Zio Software Inc., Tokyo, Japan). To understand the anatomy of the donor's vessels and design an operation plan, a picture of the vessels in and around the liver was reconstructed. RESULTS: The 3D image demonstrated two short hepatic veins next to the inferior right hepatic vein (IRHV) as well as a large IRHV. The 3D image showed a more precise diameter of the right hepatic vein (RHV) and the IRHV and a more accurate distance between the two hepatic veins than did images measured by 2-dimensional CT. This preoperative information allowed the donor surgeon to dissect the inferior vena cava (IVC) and hepatic veins with reduced blood loss because of reduced risk of injury to the blood vessels. The 3D image revealed that both the RHV and the IRHV branched off at the same angle from the cylindrical IVC. Preoperative planning based on this information secured smooth anastomosis. CONCLUSIONS: 3D visualization is useful for hepatic venous reconstruction of the recipient as well as for donor surgery in LDLT using right lobe graft.

Female↗

Transient occurrence of 27 kDa heat-shock protein in the terminal tubule cells during postnatal development of the rat submandibular gland.

It has been suggested that the 27 kDa heat-shock protein (Hsp27) plays a role at crucial cellular checkpoints for proliferation, apoptosis, and differentiation. We examined the immunolocalization of Hsp27 in the rat submandibular gland during postnatal development, wherein acinar cells proliferate and differentiate at earlier postnatal periods. At 2 weeks of age, weak Hsp27 immunoreactivity was distributed diffusely over all gland components. At 3 weeks, Hsp27 immunoreactivity disappeared in most parts of the acini and ducts, but was intensely accumulated in a small cell population located in the acinar center. This population was composed mostly of terminal tubule (TT) type I cells. At 4 weeks, the Hsp27-immunopositive cell population in the acinar center was composed primarily of immature (type II) acinar cells, partly of immature (granulated) intercalated duct (ID) cells, and occasionally of apoptotic cells. After 5 weeks, all acinar components became mature and were no longer immunoreactive for Hsp27. When acinar cell differentiation was accelerated by administration of isoproterenol to 3-week-old rats for 7 days, the number of Hsp27-positive cells was significantly lower than in the control gland at 4 weeks, confirming that Hsp27 expression is downregulated in mature acinar cells. These results suggest that at around 3-4 weeks in postnatal development, the centroacinar TT cells stop proliferating and begin to differentiate into acinar and ID cells, and occasionally undergo apoptosis. Hsp27 is transiently expressed in the centroacinar TT cells during this critical period, and thus may play a role in their differentiation into the immediate descendants.

Animals↗

Identification of ST2A1 as a rat brain neurosteroid sulfotransferase mRNA.

A hydroxysteroid sulfotransferase (ST2A1) was identified as a form mediating neurosteroid sulfation in rat brain. The sole expression among known rat ST2A forms was indicated by brain RT-PCR. All nucleotide sequences of seven ST2A cDNA clones isolated from brain matched completely with that of hepatic ST2A1. The recombinant ST2A1 protein mediated neurosteroid sulfation. These data strongly suggest a functional role of ST2A1 as a neurosteroid sulfotransferase in rat brain.

Animals↗

Propofol suppresses a hyperpolarization-activated inward current in rat hippocampal CA1 neurons.

We examined the effect of propofol and thiopental, intravenous anesthetics, on the hyperpolarization-activated inward current (I(H)), whose functional role on the neuronal activity has been evaluated. Whole-cell recordings of I(H) evoked by hyperpolarizing step pulses were taken from hippocampal CA1 neurons in rat brain slices. Propofol reduced I(H) current in a dose-dependent manner. However, thiopental had no significant effect on the activation of I(H). According to the functional role of I(H), the suppression of I(H) should result in a reduction of neuronal activity. We suggest that the effectiveness of propofol as an anticonvulsant or an antiemetic is associated with the blockade of the I(H) channel.

Anesthetics, Intravenous↗

Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide.

Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine receptors and is widely used as an anaesthetic. Recently, it has been suggested that benzodiazepines modulate cytokine responses. The purpose of the present study was to evaluate the effect of midazolam on interleukin-6 (IL-6) response by observing mRNA expression levels in human peripheral blood mononuclear cells (PBMCs) in the absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers in endotoxin-free 0.9% sodium chloride solution. The cells were incubated for 2 h at 37 degrees C immediately after isolation. IL-6 mRNA expression levels in the cells were quantified using reverse transcription and competitive polymerase chain reaction. It was found that midazolam time-dependently inhibited the IL-6 mRNA expression in PBMCs in the absence of LPS, and significantly inhibited the IL-6 mRNA expression at 1 microg/ml (P<0.05) or 10 microg/ml (P<0.01) in the absence of LPS. However, neither a specific agonist of peripheral-type benzodiazepine receptors, Ro5-4864, nor a specific agonist of central-type benzodiazepine receptors, clonazepam, inhibited IL-6 mRNA expression. These findings indicated a suppression of the IL-6 response in human PBMCs by midazolam in the absence of LPS, and suggests that midazolam has its effect not via benzodiazepine receptors, but by another mechanism.

Anti-Anxiety Agents↗

A physiological role for oxalic acid biosynthesis in the wood-rotting basidiomycete Fomitopsis palustris.

A metabolic mechanism for oxalic acid biosynthesis in the wood-rotting basidiomycete Fomitopsis palustris has been proposed on the basis of biochemical analyses of glucose metabolism. There was a strong correlation between glucose consumption and oxalate production. Oxalic acid was found to accumulate in the culture fluid in about 80% of the theoretical yield or about 5-fold, on the basis of the fungal biomass harvested. The results clearly indicate that glucose was not completely oxidized to CO(2) by the tricarboxylic acid (TCA) cycle but converted mainly to oxalate. The determination of the 12 enzymes concerned has revealed the occurrence of the unprecedented metabolic coupling of the TCA and glyoxylate cycles that support oxalate biosynthesis. In this metabolic system, isocitrate lyase (EC ), together with oxaloacetase (EC ), was found to play a pivotal role in yielding oxalate from oxaloacetate via the acetate-recycling routes. Moreover, malate dehydrogenase (EC ), with an extraordinarily high activity among the enzymes tested, was shown to play an important role in generating NADH by oxidation of malate to oxaloacetate. Thus, it is proposed that the wood-rotting basidiomycete acquires biochemical energy by oxidizing glucose to oxalate.

Basidiomycota↗

A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma.

Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is known of the molecular pathogenesis of this disease. Members of the emerging family of the CCN gene (for connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and cancer progression. Using targeted differential displays, we identified a novel variant of the CCN family member WISP1 (Wnt-induced secreted protein 1), named WISP1v, as overexpressed in scirrhous gastric carcinomas. Predicted protein of the WISP1v completely lacks a module of Von Willebrand type C that is thought to participate in protein complex formation. Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a striking cellular transformation and rapid piling-up growth. It is noteworthy that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric carcinoma cells, while wild-type WISP1 had no such potential. These findings suggest that CCN protein WISP1v is involved in the aggressive progression of scirrhous gastric carcinoma.

3T3 Cells↗

Promoter structure and gene expression of the mouse inositol 1,4,5-trisphosphate receptor type 3 gene.

Inositol 1,4,5-trisphosphate receptor type 3 (IP(3)R3) is a ubiquitously expressed IP(3)R gene in the IP(3)R gene family. We identified an upstream region of the mouse IP(3)R3 genomic DNA. Transcription start points for the IP(3)R3 gene were found to be located mainly at four sites between nucleotide position -325 and -285 relative to the first ATG codon. The major start point was mapped around -325. Transcription promotion ability was detected between -325 and -285 in an IP(3)R3 proximal promoter sequence. The promoter had no TATA-box but was highly GC-rich and contained two putative Sp1-binding sites. There was no sequence similarity between promoter regions of IP(3)R3 and IP(3)R2, another ubiquitous gene, except for GC-boxes. By using a series of 5'-truncation versions and a transient luciferase assay, we detected multiple common and cell-type-dependent regulatory regions within the distal promoter sequence downstream from -4.0 kb that function positively or negatively. The IP(3)R3 gene was highly transcribed in the kidney, spleen, heart, and skeletal muscle, and this tissue distribution pattern was nearly complementary to that of IP(3)R2. We found that IP(3)R3 gene expression was repressed in retinoic acid-treated and neural differentiated P19 mouse embryonic carcinoma cells.

3T3 Cells↗

Risk of Toxoplasma gondii infection in slaughterhouse workers in Kitakyushu City.

To clarify the risk of Toxoplasma gondii infection among slaughterhouse workers, we investigated Toxoplasma antibody in workers and swine in the meat center of Kitakyushu City and discussed the result from the standpoint of working conditions. Among 67 slaughterhouse workers, 22 were positive for Toxoplasma antibody (positive rate, 32.8%), while among 208 swine, 19 were positive (positive rate, 9.1%). When classified by ages of workers, positive rates in workers were 0% at the age of 30 or less and around 40% at the age of 31 and over. Especially, positive rate became as high as 66.7% in workers aged 61 and over. Positive rates for Toxoplasma antibody in workers classified by duration of employment were 25% for 5 years or less and 41.5% for 6 years and over. Moreover, there was no difference in positive rates of Toxoplasma antibody between swine slaughterers (positive rate, 32.4%) and cattle slaughterers (33.9%). Although overall positive rate of Toxoplasma antibody in slaughterers was higher, positive antibody in younger slaughterers or that of shorter duration of employment was considerably low. In addition, since positive rate of Toxoplasma antibody in swine brought to the slaughterhouse has decreased remarkably in comparison to the previous study, risk of toxoplasmosis in slaughterhouse workers also seemed to have decreased.

Abattoirs↗

Survival of boar spermatozoa frozen in diluents of varying osmolality.

We investigated the effects of freezing diluents of differing levels of osmolality on boar sperm cryosurvival. The spermatozoa were frozen using a pellet technique. Cryosurvival was evaluated in terms of motility, intact acrosomes and membrane integrity. The motility parameters were assessed using a computer-assisted sperm motility analysis (CASA) system. Acrosomal status was monitored by means of FITC-labeled peanut agglutinin, and membrane integrity was evaluated after double staining with SYBR-14 and propidium iodide. At 3 h of incubation after thawing, the highest motility was found in the 420 mOsm/kg group, and progressive motiLity in the 420 to 580 mOsm/kg groups was higher than that in the hypo- (225 mOsm/kg) and iso-osmotic (290 mOsm/kg) groups (P < 0.05). The intact acrosomes of the spermatozoa frozen in the 510 and 580 mOsm/kg BF5 diluents were more numerous than in other groups (P < 0.05). The 420 and 510 mOsm/kg groups yielded maximal values of post-thaw membrane integrity. These observations obtained in the present study indicate that moderately hypertonic BF5 diluents are favorable for the cryopreservation of boar spermatozoa.

Acrosome Reaction↗

Expression of a tumor-associated antigen RCAS1 in hepatocellular carcinoma.

RCAS1 has been reported as a tumor-associated antigen in uterine and ovarian carcinomas. In vitro studies on RCAS1 indicated that it might function as an apoptosis-inducing factor since binding between RCAS1 and its receptor induced apoptosis in receptor-expressing cells. In this study, 68 surgically resected samples of hepatocellular carcinoma (HCC) were prepared and RCAS1 expression was examined immunohistochemically, because RCAS1 was also positive in all HCC cell lines tested. Clinical and pathological parameters were then compared between RCAS1-positive and -negative HCC cases. As a result, RCAS1 is expressed in 26.5% of HCC cases and vascular invasion is observed at a much higher rate in the RCAS1-positive cases (72.2%) than in RCAS1-negative cases (24.0%). RCAS1 is not an antigen specific for gynecological cancers. In HCC cases, the RCAS1-positive percentage is not high, however, RCAS1-positive HCCs exhibited a trend towards invasive character.

Animals↗

TBP-like protein (TLP/TLF/TRF2) artificially recruited to a promoter stimulates basal transcription in vivo.

Metazoan genomes generally contain one TBP-related gene designated as TBP-like protein (TLP/TLF/TRF2). Although TLP is thought to work for transcriptional regulation, its natural function has not been clearly demonstrated. Here we describe the stimulation of transcription from TATA-containing and TATA-less class II promoters by artificially recruited mammalian TLP. TLP fused with Gal4 DNA-binding domain stimulated transcription when it was recruited at a proximal promoter. Compared to TBP, stimulation by TLP was less TATA-dependent. Slight truncation from each terminus of TLP destroyed this function drastically. Amino acid substitutions of TLP whose corresponding residues in TBP are crucial for its function resulted in the loss of function. Consequently, Gal4-fused TLP was demonstrated to exhibit ability of transcription activation irrespective of the type of promoter, the mechanism of which was thought to be similar to that of artificially recruited TBP. TLP is presumably able to behave as a transcriptional activator in cells.

Amino Acid Substitution↗

Liver metastasis from gallbladder carcinoma: anatomic correlation with cholecystic venous drainage demonstrated by helical computed tomography during injection of contrast medium in the cholecystic artery.

BACKGROUND: The current study evaluated whether the sites of liver metastasis from gallbladder carcinoma are correlated with areas of cholecystic venous drainage (CVD) utilizing helical computed tomography (CT) during the injection of contrast medium into the cholecystic artery (cholecystic artery CT). METHODS: Cholecystic artery CT scans were performed in 26 patients with gallbladder carcinoma. Liver metastases were examined retrospectively in these patients on CT, and the sites of liver metastasis and CVD were compared closely. The patients were divided into concurrent (those who had metastasis at the time of cholecystic artery CT), early postoperative metastasis (those who developed metastasis within 6 months after surgery), and late postoperative metastasis (those who developed metastasis more than 6 months after surgery) groups. The frequency of metastasis related to CVD was compared between the three groups. RESULTS: A total of 32 metastases were identified in 11 patients, 21 of which were related to CVD. Six patients were included in the concurrent metastasis group; 18 of 20 tumors were found to be related closely to CVD. There were two patients in the early postoperative metastasis group; all three of the tumors detected were found to be closely related to CVD. Three patients were subclassified as being in the late postoperative metastasis group; none of the nine tumors detected appeared to be in areas associated with CVD. CONCLUSIONS: The sites of liver metastases were found to be well correlated with the areas with CVD, particularly in the concurrent and early postoperative metastasis groups. CVD may be a useful marker of potential areas of liver metastasis from gallbladder carcinoma, particularly in patients with early stage metastasis.

Adult↗

Telomerase activity and p53-dependent apoptosis in ovarian cancer cells.

We conducted the present study to determine the relationship between p53-dependent apoptosis and telomerase activity in ovarian cancer cells. A human ovarian adenocarcinoma cell line, SK-OV-3 that had homozygous deletion of the p53 gene was used in this study. Wild-type p53 genes were transducted to SK-OV-3 cells with a recombinant adenovirus that contained a wild-type p53 gene (AxCAp53). IC(50)to cisplatin (CDDP) was 12.9 microM for SK-OV-3 cells and 9.2 microM for p53 gene-transducted SK-OV-3 cells. The apoptotic index for cells with p53 gene transduction was significantly higher than cells without transduction. Additionally, p53 gene transduction significantly enhanced CDDP-induced apoptosis. Bax protein in SK-OV-3 cells did not differ before and after exposure to CDDP. In SK-OV-3 cells with transduction of the p53 gene, the expression of p53 and Bax proteins increased after exposure to CDDP. Expression of Bcl-xL decreased after exposure to CDDP in SK-OV-3 cells with and without transduction. The telomerase activity in SK-OV-3 cells with the p53 gene was significantly lower compared with the cells without the p53 gene. CDDP exposure did not affect telomerase activity and human telomerase reverse transcriptase (hTERT) expression in both cell lines. We suggest that the p53 gene may relate to telomerase activity, but that p53-dependent apoptosis does not affect the activity.

Adenocarcinoma↗

Laparoscopic hepatectomy for hepatocellular carcinoma.

BACKGROUND: No reports exist on the role of laparoscopic hepatectomy in the short- and long-term outcomes of patients with hepatocellular carcinoma (HCC). We present our results from using laparoscopic hepatectomy for HCC and discuss the importance of this procedure. METHODS: To investigate the role of laparoscopic hepatectomy in the short- and long-term outcomes, 17 patients with HCC who underwent laparoscopic hepatectomy (laparoscopic hepatectomy group) were compared with 38 patients who underwent conventional open hepatectomy (open hepatectomy group) during the same period. RESULTS: No differences in operation time, blood loss, rate of blood transfusion, or incidence of postoperative complications were found between the two groups. The postoperative hospital stay for the laparoscopic hepatectomy group was significantly shorter than for the open hepatectomy group. With long-term prognosis, no difference was found in survival rate and disease-free survival rate between the two groups. No recurrence was found in the stump of the remaining liver after laparoscopic hepatectomy. CONCLUSIONS: Laparoscopic hepatectomy has resulted in a better short-term outcome after surgery than conventional open hepatectomy. The long-term prognosis in the laparoscopic hepatectomy group was similar to that in the open hepatectomy group. Therefore, laparoscopic hepatectomy can be a new alternative for treatment of cirrhotic patients with HCC when patients are strictly selected.

Carcinoma, Hepatocellular↗

Cytokine characteristics of jaundice in mouse liver.

OBJECTIVE: The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. MATERIALS AND METHODS: Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. RESULTS: The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. CONCLUSIONS: In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.

Animals↗

Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model.

Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene. The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by s.c. implantation of MH134 cells to C3H mice. This process made use of plasmid DNA that express the luciferase gene. We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC. In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found. These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial.

Animals↗

Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial.

HYPOTHESIS: Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection. DESIGN: A prospective randomized trial. SETTING: A university hospital department of surgery. PATIENTS: Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery. MAIN OUTCOME MEASURES: Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured. RESULTS: Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications. CONCLUSIONS: Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.

Acute-Phase Proteins↗