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Biomedical subjects

Y Shoji

Publications and source records attributed to Y Shoji.

At least 73 records · Page 4Linked to original sources

[Trend in genetic medicine].

Genetic medicines including antigen, antisense molecules, ribozymes, aptamers, plasmid, gene have been enthusiastically studied as pharmaceutical agents. In the past decade, genetic medicines have been bogged down in solving serious problems, especially delivery efficiency. Steady study are continued to apply chemical modifications, cationic liposomes or another drug carriers enhance biological activities of genetic medicines. At this current moment, some of them have been carried on in clinical stages, which are intriguing to keep attention on the results coming soon. In this review, we address the current trends in genetic medicines especially antisense oligonucleotides and aptamers.

Animals↗

Noninvasive quantitation of cerebral blood flow using oxygen-15-water and a dual-PET system.

UNLABELLED: Measurement of the arterial input function is essential for quantitative assessment of physiological function in vivo using PET. However, frequent arterial blood sampling is invasive and labor intensive. Recently, a PET system has been developed that consists of two independent PET tomographs for simultaneously scanning the brain and heart, which should avoid the need for arterial blood sampling. The aim of this study was to validate noninvasive quantitation with this system for 15O-labeled compounds. METHODS: Twelve healthy volunteers underwent a series of PET studies after C15O inhalation and intravenous H2(15)O administration using a Headtome-V-Dual tomograph (Shimadzu Corp., Kyoto, Japan). The C15O study provided gated blood-pool images of the heart simultaneously with quantitative static blood-volume images of both the brain and heart. Weighted-integrated H2(15)O sinograms were acquired for estimating rate constant (K1) and distribution-volume (Vd) images in the brain, in addition to single-frame sinograms for estimating autoradiographic cerebral blood flow images. Noninvasive arterial input functions were determined from the heart scanner (left ventricular chamber) according to a previously developed model and compared directly to invasive input functions measured with an on-line beta probe in six subjects. RESULTS: The noninvasive input functions derived from this PET system were in good agreement with those obtained by continuous arterial blood sampling in all six subjects. There was good agreement between quantitative values obtained noninvasively and those using the invasive input function: average autoradiographic regional cerebral blood flow was 0.412 +/- 0.058 and 0.426 +/- 0.062 ml/min/g, K1 of H2(15)O was 0.416 +/- 0.073 and 0.420 +/- 0.067 ml/min/ml and Vd of H2(15)O was 0.800 +/- 0.080 and 0.830 +/- 0.070 ml/ml for the noninvasive and invasive input functions, respectively. In addition to the brain functional parameters, the system also simultaneously provided cardiac function such as regional myocardial blood flow (0.84 +/- 0.19 ml/min/g), left ventricular volume (132 +/- 22 mm at end diastole and 45 +/- 14 ml at end systole) and ejection fraction (66% +/- 5%). CONCLUSION: This PET system allows noninvasive quantitation in both the brain and heart simultaneously without arterial cannulation, and may prove useful in clinical research.

Adult↗

In vivo induction of murine cytokine production by carcinoembryonic antigen.

Carcinoembryonic antigen (CEA) may promote experimental metastasis through production of cytokines. The effect of systemic CEA on the production of proinflammatory cytokines was investigated in mice and compared to levels induced by lipopolysaccharide (LPS). Serum concentrations of interleukin (IL)-6 peaked 1 h after an i.v. CEA injection of 40 microg/mouse to 37-54% of the maximal level induced by a 1 microg/mouse injection of LPS in both normal and immunoincompetent mice. The CEA induction of IL-6 was a specific response, because the peptide PELPK (the pentapeptide on CEA that is the ligand for the CEA receptor on Kupffer cells) conjugated to albumin induced 30% of the maximal CEA response for IL-6, whereas the specificity control PELGK-conjugated albumin did not. IL-1alpha and tumor necrosis factor (TNF)-alpha levels after i.v. injection of CEA were only 3-5% of those induced by LPS. The IL-6 responses of mice pretreated with 100 microg/kg genistein were decreased by more than 40%. However, genistein inhibited the TNF-alpha response to LPS by 46% but increased the CEA-induced response by 300%. When murine Kupffer cells were stimulated with LPS or CEA in vitro, LPS increased tyrosine phosphorylation of a Mr 30,000 protein, whereas CEA decreased phosphorylation of a Mr 60,000 protein and did not increase phosphorylation of the Mr 30,000 protein. Thus, i.v. CEA stimulates production of IL-6 and TNF-alpha after binding to Kupffer cells through signal transduction pathways that appear to be different from those stimulated by LPS.

Animals↗

Perforation of acalculous cholecystitis associated with localized atherosclerosis: report of a case.

We describe herein the unusual case of a 68-year-old Japanese man who underwent laparotomy for an acute abdomen caused by diffuse peritonitis, which revealed perforation of the gallbladder without any stones. A cholecystectomy was subsequently carried out, and histological examination showed marked atherosclerosis of the gallbladder associated with acute inflammatory changes. It is most likely that circulatory disturbance of the gallbladder wall due to the atherosclerosis played an important role in the events leading to perforation. Acute acalculous cholecystitis is an uncommon condition which is extremely difficult to diagnose preoperatively. The clinicopathological features of this patient are of particular interest and importance in terms of pathogenesis as well as treatment.

Acute Disease↗

Functional results after "high" coloanal anastomosis and "low" coloanal anastomosis with a colonic J-pouch for rectal carcinoma.

The aim of this study was to determine the postoperative function of neorectoanal components using two different types of very low coloanal reconstruction. The two groups of patients assessed were 22 who underwent abdominal rectal resection and stapled "high" coloanal anastomosis without a pouch, being the HCAA-P group; and 34 who underwent anoabdominal rectal resection and "low" coloanal anastomosis with a colonic J-pouch, being the LCAA + P group. Manometric examination was performed 1, 3, 6, and 12 months postoperatively, and the patients were also assessed by a questionnaire. The LCAA + P group had remarkably less daily stool frequency and urgency, but there were no significant differences in the other functional parameters. Maximum resting pressure (MRP) was significantly less, while threshold volume (TV) and maximum tolerable volume (MTV) were greater in the LCAA + P group than in the HCAA-P group. The colonic J-pouch compensated for decreased MRP. Thus, when HCAA-P is performed, 3.0 cm of residual rectum with internal anal sphincter may be required, and construction of the pelvic pouch is desirable in low coloanal anastomosis.

Adult↗

Stapled fistulectomy to treat enteroenteric fistulas in Crohn's disease.

We report herein our technique of performing stapled fistulectomy as minimum surgery for the resection of nine entero-enteric fistulas in six patients with Crohn's disease. The surgical outcome was successful in all patients. It would seem that fistulous sites without a severe affected lesion are a favorable indication for this procedure and we recommend this simplified fistulectomy for selected conditions in Crohn's disease.

Adult↗

Active hypothalamic-pituitary-gonadal axis in an infant with X-linked adrenal hypoplasia congenita.

To evaluate the hypothalamic-pituitary-gonadal axis in an infant with adrenal hypoplasia congenita, we measured the serum levels of testosterone and performed a luteinizing hormone-releasing hormone stimulation test. The diagnosis was made because of the presence of a mutation, A300V, in the DAX-1 gene. The results demonstrated an active hypothalamic-pituitary-gonadal axis, with adult-level testosterone of 266 ng/dl on day 0, and maintenance of testosterone concentration in the 100 to 250 ng/dl range for 140 days as expected. The luteinizing hormone-releasing hormone lest was compatible with an active pituitary gland with a luteinizing hormone peak of 13.1 IU/L and a follicle-stimulating hormone of 5.0 IU/L We conclude that the DAX-1 mutation does allow a normal reproductive axis at birth. We speculate that sometime between infancy and puberty this mutation in the DAX-1 gene leads to an inability to activate the reproductive axis from its childhood suppression; thus puberty will not develop in this infant.

Adrenal Insufficiency↗

Detection of the Epstein-Barr virus genome in cervical neoplasia is closely related to the degree of infiltrating lymphoid cells: a polymerase chain reaction and in situ hybridization approach.

To cast light on the significance of Epstein-Barr virus (EBV) infection in cervical tumorigenesis, 44 cervical intraepithelial neoplasia (CIN) types I/II, and 70 CIN III lesions, 60 invasive squamous cell carcinomas (ISCC), and 20 normal cervical samples were investigated by polymerase chain reaction (PCR) and RNA in situ hybridization (RISH) assays. The EBV genome was detected by PCR using primers targeting the IR region in three (6.8%) of the CIN I/II, 15 (21.4%) of the CIN III and 13 (21.7%) of the ISCC lesions, while using an EBER oligonucleotide probe RISH revealed positive signals in infiltrating lymphocytes located in the cervical stroma, but not in dysplastic or tumor cells. There was a significant correlation between the presence of EBV DNA and the degree of lymphoid cell infiltration (P = 0.0223). In contrast, none of the normal cervical samples that were without inflammation demonstrated any EBV infection. Thus, the results indicated that a positive result for EBV on PCR may be simply dependent on the amount of lymphocytes in cervical stroma, suggesting that this virus does not play a major role in the etiology of cervical neoplasia.

Carcinoma, Squamous Cell↗

Working pressure for full balloon inflation during intraaortic balloon pumping.

With changes in heart rate and mean aortic pressure, an intraaortic balloon (IAB) works with incomplete inflation. The effects of initial peak positive pressure and plateau holding positive pressure on IAB volume were investigated and minimum pressures necessary to inflate an IAB to a desired volume were established with a standard IAB catheter (Datascope type, 9.5 Fr, 40 ml). Initial peak pressure greater than 200 mm Hg was adequate to attain the desired volume of the IAB. Plateau positive pressure should be altered in accordance with hemodynamic changes.

Analysis of Variance↗

Factors that reverse the persistent depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro.

In CA1 pyramidal neurons in rat hippocampal tissue slices, superfusion with ischemia-simulating medium produced a rapid depolarization after 6 min of exposure. The membrane potential eventually reached 0 after 5 min (a persistent depolarization), even when oxygen and glucose were reintroduced. The role of various ions in the reversal of this persistent depolarization after reintroduction of oxygen and glucose was investigated. The peak of the persistent depolarization was decreased in solutions containing reduced Na+ or Ca2+ and in solutions containing Co2+ or Ni2+. In contrast, the depolarization was not affected by reduction of external K+ or Cl- or by addition of tetrodotoxin (TTX), flunarizine, or nifedipine. These results suggest that sustained Na+ and Ca2+ influxes produce the persistent depolarization. The membrane potential recovered after reintroduction of oxygen and glucose in low Ca2+, low Cl-, or K+-rich medium and in TTX- or tetraethylammonium-containing medium, but not in low Na+ or low K+ medium and in flunarizine- or nifedipine-containing medium. Either reduction in extracellular Ca2+ or addition of Co2+ was the most effective in promoting recovery from the persistent depolarization, suggesting that Ca2+ influx has a key role in causing the membrane dysfunction. The peak of the persistent depolarization was reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), DL-2-amino-5-phosphonopentanoic acid (AP5), DL-amino-3-phosphonopropionic acid (AP3), or DL-amino-4-phosphonobutyric acid, suggesting that activation of non-N-methyl-D-aspartate (non-NMDA), NMDA, and metabotropic glutamate (Glu) receptors is involved in the generation and maintenance of the persistent depolarization. Among these Glu receptor antagonists, only CNQX or AP5 was able to reduce dose dependently the level of depolarization, suggesting that Ca2+ influx via both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate type II receptors and NMDA receptors contributes to the membrane dysfunction. trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) did not affect the peak potential of the persistent depolarization, but it dose-dependently restored the membrane potential. AP3 antagonized the protective action of t-ACPD. The membrane potential also recovered after reintroduction when the slice was pretreated by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, ryanodol 3-(1H-pyrrole-2-carboxylate), 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride, and procaine, suggesting that raised [Ca2+]i from Ca2+-induced Ca2+ release pool contributes to the membrane dysfunction. It, therefore, is concluded that raised [Ca2+]i has a dominant role in causing irreversible changes. The increase in [Ca2+]i during the persistent depolarization may be the result of Ca2+ entry via both a leaky membrane and Glu-activated receptor channels as well as Ca2+ released from internal stores.

Animals↗

Characterization, cell uptake, and subcellular distribution of DNA complexes with lipoglutamides having tetraethylene glycol tails.

Lipoglutamides with tetraethylene glycol tails were synthesized. Physicochemical features of the DNA/lipoglutamide complexes were investigated by light scattering method, phase transition, and CD-spectrum. Aggregation of the DNA/lipoglutamide complex was significantly depressed compared with DNA complexes without ethylene glycol tails, and the solution showed no turbidity. The DNA/lipoglutamide complex showed a high resistance to nuclease, and an efficient internalization into tumor cells, compared with those of DNA alone. Furthermore, the DNA complex was found by confocal laser scanning fluorescence microscopy to distribute in the cytoplasmic region.

Biocompatible Materials↗

Inhibition of collagenases from mouse lung carcinoma cells by green tea catechins and black tea theaflavins.

Theaflavin and theaflavin digallate, which are components of black tea were examined by in vitro invasion assay with mouse Lewis lung carcinoma LL2-Lu3 cells, which are highly metastatic. The compounds inhibited invasion by the tumor cells. Gelatin zymography showed that the cells secreted matrix metalloproteinases (MMPs), probably including MMP-2 and MMP-9, which may be involved in tumor cell invasion and metastasis. Theaflavin and theaflavin digallate also inhibited MMPs from the culture medium of these tumor cells, as did (-)-epigallocatechin gallate. These results suggest that theaflavin, theaflavin digallate, and (-)-epigallocatechin gallate inhibit tumor cell invasion by inhibiting type IV collagenases of the LL2-Lu3 cells.

Animals↗

[Effects of pre-operative administration of steroids on the serum interleukin (IL)-6, IL-8 and organ injuries in replacement of thoracic aorta].

To investigate whether pre-operative steroids administration decreases the post-operative serum IL-6, IL-8 and prevents organ injuries, we prospectively studied patients undergoing elective replacement of thoracic aorta using an extracorporeal circulation. Six of 10 patients (group S) were pretreated with methylprednisolone 500 mg 2 hours before operation while the other 4 patients (group C) were not. Though post-operative serum IL-6, IL-8, C-reactive protein and amylase elevated in group C, the elevations were significantly decreased in group S (p < 0.05). These findings show that in replacement of thoracic aorta, pre-operative steroid administration decreases the post-operative elevations of serum inflammatory cytokines (IL-6 and IL-8) and may prevent organ injuries.

Aged↗

[Redo operation after surgery for aortic aneurysm and dissection].

Thirteen patients who underwent redo operation after surgical treatment of aortic aneurysm and dissection were presented. In 8 patients, redo operations were performed for aortic dissection following aortic valve replacement. A-C bypass, the Koster-Collins operation and replacement of thoracic aorta. In the other 5 patients, the reasons for redo operation were aortic root enlargement after replacement of ascending aorta and aortic valve replacement, pseudoaneurysm and aneurysmal dilatation around coronary button for the Bentall operation and recurrent aneurysm after patch aortoplasty and thoracoabdominal replacement using the Crawford's maneuver. To prevent these redo operation, adequate selection of surgical procedures and meticulous operative techniques should be required in primary operation.

Aortic Dissection↗

Anoabdominal rectal resection and colonic J pouch-anal anastomosis: 10 years' experience.

BACKGROUND: Coloanal anastomosis and radiotherapy for the treatment of lower rectal carcinoma have been receiving increasing attention. METHODS: Patients with rectal cancer were divided into two groups: anoabdominal rectal resection and colonic J pouch-anal anastomosis (CAA) plus preoperative intraluminal brachytherapy (IBT) (group 1; 68 patients) and CAA without IBT (group 2; 23 patients). Group 3, comprising 59 patients who underwent abdominoperineal excision (APE), was examined as a control group. Comparative results were reviewed. RESULTS: Postoperative complications occurred more frequently in group 1 than in group 2. Actuarial 5-year survival rates were 73 per cent in group 1, 64 per cent in group 2 and 63 per cent in group 3. Cumulative local recurrence rates at 5 years were 11 per cent in group 1, 38 per cent in group 2 and 21 per cent in group 3. Intestinal continuity breakdown was seen in 14 per cent of all patients at 5 years after initial operation. CONCLUSION: The combination of CAA and preoperative IBT resulted in decreased local recurrence. IBT followed by CAA can be a good restorative option for combating lower rectal cancer.

Adult↗

Analysis for the subcellular distribution of oligonucleotide/lipid complexes.

We synthesized a lipoglutamide having tetraethylene glycol tails (PEG lipid), and prepared a DNA/PEG lipid complex. Observation by a confocal laser scanning fluorescence microscope showed that the oligonucleotide/PEG lipid complex distributed in cytoplasmic region. On the other hand, a oligonucleotide/lipofectin complex distributed in nucleus. Interactions of the oligonucleotide complexes with isolated nucleus were also investigated, and mechanisms of the subcellular distributions were discussed.

Animals↗