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Biomedical subjects

T Tani

Publications and source records attributed to T Tani.

At least 235 records · Page 13Linked to original sources

[A case of true thymic hyperplasia showing slow growth as revealed by chest X-ray].

A case of true thymic hyperplasia in a 33-year-old man is reported. Radiographic findings of the chest (including computer tomography and magnetic resonance imaging) showed a mass in the anterior mediastinum. Thoracotomy revealed an enlarged thymus. Histological examination identified true thymic hyperplasia. True thymic hyperplasia is a lesion rarely observed in adults. This case was reported because of the age of the patient.

Adult↗

[The spinal cord evoked potential by computer simulation: elucidation of killed-end potentials and augmentation caused by the conduction block phenomenon].

Single nerve fiber action potential (single-NAP) was computer simulated using solid angle approximation theory. The simulated spinal cord evoked potential (Simulated-SCEP) was then produced by summing the simulated single-NAPs according to the data of the fiber diameter spectrum of the human spino-cerebellar tract. To model the conduction block phenomenon in the spinal cord, it was assumed that each fiber impulse which reached the conduction block point could not go through the point and gradually became smaller. When the largest 10% of the constituent fibers had become blocked, there was augmentation of the negative peak at just before the conduction block point and at every point after the block. As the percentage of the blocked fibers increased, the amplitude of the simulated-SCEP decreased at every point except at just before the block. When 50% or more of the largest fibers were blocked, then augmentation of the negative peak still remained at just before the conduction block. However at the points just after the conduction block there was a monophasic positive waveform which is known as the killed-end potential. Phase cancellation normally dictates the wave forms of compound action potential. However, the killed-end potential and the augmentation of the amplitude associated with the conduction block can be explained by the loss of the phase cancellation.

Action Potentials↗

10(6) Depletion of WBC with CF-2, a new leukocyte removal filter.

A new leukocyte removal filter, Nipro CF-2, was evaluated. A non-woven polyester filter, gravity flow device that does not require priming and rinsing after use was developed to remove white blood cells from 400 ml of whole blood or concentrates of 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low WBC counts. To evaluate the efficiency of this filter, leukocyte counts were measured by flow cytometry using a Coulter EPIC-C cytometer. After filtration through a CF-2 filter, more than 99.9999% of WBCs were depleted from 6 of 17 samples. The mean value of WBC depletion was 99.9994%. The CF-2 filter achieved nearly a million-fold depletion of WBCs from whole blood concentrates.

Cell Separation↗

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study.

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group. The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p = 0.074; generalized Kruskal-Wallis, p = 0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Kruskal-Wallis, p = 0.045). No side effects attributable to SPG were recorded. The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.

Adjuvants, Immunologic↗

Treatment of septic shock with a protease inhibitor in a canine model: a prospective, randomized, controlled trial.

OBJECTIVES: To evaluate the efficacy and mechanism of action of a protease inhibitor (ulinastatin) in septic shock. DESIGN: Prospective, randomized, controlled trial. SETTING: A university laboratory. SUBJECTS: Twelve mongrel dogs. INTERVENTIONS: One of the protease inhibitors, ulinastatin, a glycoprotein (molecular weight 67,000 daltons) detected in human urine was estimated. We used Escherichia coli to obtain a model of septic shock in dogs in vivo study. Human neutrophils were used as an activating target in vitro. MEASUREMENTS AND MAIN RESULTS: The final concentration of E. coli was 1.9 x 10(6) colony-forming units/mL. There was no significant difference in E. coli concentration between ulinastatin-treated and control groups. Human neutrophils treated with 100 U/mL of ulinastatin showed 70.5% to 78.7% of the superoxide production or untreated neutrophils. Phagocytic activity was enhanced in a dose-dependently manner by ulinastatin. At a ulinastatin concentration of 100 U/mL, an approximate two-fold increase in activation was found. In the ulinastatin-treated group, cardiac index, blood pressure, lactic acid, blood glucose, and blood base values significantly improved 60 mins after ulinastatin administration, and the bacterial count was significantly decreased, while the endotoxin concentration in the control group showed a continuous increase of endotoxin concentration. The improvement in the monitored factors observed 60 mins after initiation of treatment persisted after the end of treatment. The survival rate after 1 wk in the ulinastatin-treated group was 84% (five of six dogs survived), while it was 16% (one of six dogs survived) in the control group (p = .04). CONCLUSIONS: Ulinastatin does not have antimicrobial activity, and it does not sufficiently activate phagocytes. It is suggested that the efficacy of this agent in experimental septic shock is due to a mechanism that activates the reticuloendothelial system and septic reactions.

Adult↗

An mRNA-type intron is present in the Rhodotorula hasegawae U2 small nuclear RNA gene.

Splicing an mRNA precursor requires multiple factors involving five small nuclear RNA (snRNA) species called U1, U2, U4, U5, and U6. The presence of mRNA-type introns in the U6 snRNA genes of some yeasts led to the hypothesis that U6 snRNA may play a catalytic role in pre-mRNA splicing and that the U6 introns occurred through reverse splicing of an intron from an mRNA precursor into a catalytic site of U6 snRNA. We characterized the U2 snRNA gene of the yeast Rhodotorula hasegawae, which has four mRNA-type introns in the U6 snRNA gene, and found an mRNA-type intron of 60 bp. The intron of the U2 snRNA gene is present in the highly conserved region immediately downstream of the branch site recognition domain. Interestingly, we found that this region can form a novel base pairing with U6 snRNA. We discuss the possible implications of these findings for the mechanisms of intron acquisition and for the role of U2 snRNA in pre-mRNA splicing.

Base Sequence↗

Estimation of infarct size using serum troponin T concentration in patients with acute myocardial infarction.

To estimate the size of myocardial infarction, serum troponin T concentration was measured in 34 patients with acute myocardial infarction. Left ventriculography, 2-dimensional echocardiography and resting 201thallium myocardial single photon emission computed tomography (SPECT) were performed about 4 weeks after the onset of myocardial infarction and used for correlation with the late serum troponin T peak concentration which occurred on the 3rd to 5th day after onset. Both left ventricular ejection fraction (LVEF) obtained from left ventriculography and wall motion index (WMI) obtained from 2-dimensional echocardiography were inversely related to late troponin T peak value (LVEF: r = 0.68, p < 0.001, WMI: r = 0.70, p < 0.001). Extent score (ES) and severity score (SS), which were estimated from the initial resting 201thallium SPECT image, showed excellent linear correlations with late troponin T peak concentrations (ES: r = 0.77, p < 0.001, SS: r = 0.66, p < 0.001). This correlation was present both in patients with an early troponin T peak on day 1 (group A-16 patients) and in those without an early peak (group B-10 patients). Thus, late troponin T peak concentration can be used to predict infarct size regardless of the kinetics of its appearance in serum.

Adult↗

[Therapeutic plasmapheresis to treat postoperative hepatic failure clinical course and therapeutic outcome in Japan].

The most serious hepatic complication after surgical procedure is postoperative hepatic failure. There is no therapy for this condition except plasma exchange. Precise clinical definition of postoperative hepatic failure was discussed based on a questionnaire distributed by the association in 1989, and in 1991 by the working group. Giving special consideration to the use of therapeutic plasmapheresis, the clinical definition of postoperative hepatic failure was established as hepatic injury after surgery, without obstructive causative factors, laboratory values for total bilirubin over 5mg/dl with continuous elevation, and hepaplastin activity under 40%. Key factors in determining initiation, efficacy, and cessation of plasmapheresis were coma grade (II-III), total bilirubin levels, and the activities of coagulation tests. The majority of underlying diseases were hepato-biliary in nature. The causative factors of hepatic injuries were massive bleeding and infection. The morbidity was estimated at 600 to 3000 cases/year. The frequency of plasma exchange was one session every/1.4-1.6 days. The volume of exchanged fresh frozen plasma was about 3292 ml/a session. Nafamostat mesilate was used as an anticoagulant. The survival rate was 14% to 40%. Earlier initiation of plasma exchange is indicated.

Benzamidines↗

[Treatment of sepsis by extracorporeal elimination of endotoxin using fiber-immobilized polymyxin B].

To remove endotoxin directly from the blood, an affinity adsorbent (PMX) has been developed. PMX is composed of a ligand of polymyxin B and a carrier of polystyrene fibers. We treated 16 patients, suffering from septic shock or multiple organ failure by PMX-F hemoperfusion. The pretreatment level of endotoxin decreased significantly from 80pg/ml to 21pg/ml on average 2 hours after the hemoperfusion. The hyperdynamic status in the cardiac index and the decreased systemic vascular resistance, which are characteristic to endotoxin shock, were normalized after the treatment. In septic shock patients with systolic pressure under 10mmHg, the systolic pressure increased significantly from pretreatment level. Nine of the sixteen patients remained alive for two weeks after the therapy, and seven out of the nine patients discharged alive. Hemoperfusion with PMX is likely to become an effective treatment for sepsis and septic shock.

Endotoxins↗

[Prevention of postoperative recurrence after hepatic resection for metastatic colorectal cancer by adjuvant locoregional chemotherapy].

Postoperative adjuvant locoregional chemotherapy was performed on patients who underwent hepatic resection for metastatic colorectal cancer. To prevent recurrence in the residual liver after hepatic resection. 7 patients received intra-hepato-arterial infusion of MMC, 5-fluorouracil (5-FU), doxorubicin + Lipiodol emulsion. Sixteen cases did not receive such treatment. The 1-, 2- and 3-year cumulative disease free rates were 100, 80 and 40% in the patients with this adjuvant chemotherapy, against 61.4, 54.6 and 28.1% in those without this locoregional therapy, respectively. The 1-, 2- and 3-year cumulative survival rates were 100, 100 and 60% in the TAI-E group, and 73.7, 63.3 and 63.3% in the patients without TAI-E, respectively. Postoperative adjuvant locoregional chemotherapy is considered effective to prevent the recurrence of metastatic colorectal cancer in the residual liver after hepatectomy.

Aged↗

[Evaluation of the combination of chemotherapy with etoposide, adriamycin and cisplatin (EAP) in advanced or recurrent gastric cancer].

EAP therapy was performed on 30 cases of advanced or recurrent gastric cancer between September 1987 and July 1991. The clinical responses of 15 trial patients were evaluated. The overall response rate was 40.0% (CR, one case; PR 5 cases). The results were thus not as favorable as that reported by Preusser et al. On the contrary, with such a poor response rate, this treatment did not lead to a prolonged life span (mean survival time; 5.6 months, median survival time; 4 months). Side effects, such as myelosuppression, appetite loss, nausea, vomiting, liver dysfunction, renal dysfunction, and alopecia, were also observed. Myelosuppression was a dose-limiting factor. The rhG-CSF proved in 4 cases to be a clinically useful tool against the neutropenia induced by this treatment. It may be concluded that EAP should be given to the following selected patients: (1) those whose condition is not so far advanced: (2) those who have not received many other forms of treatment; and (3) those in excellent general physical condition.

Adult↗

Activity of chimeric RNAs of U6 snRNA and (-)sTRSV in the cleavage of a substrate RNA.

U6 small nuclear RNA is one of the spliceosomal RNAs essential for pre-mRNA splicing. Discovery of mRNA-type introns in the highly conserved region of the U6 snRNA genes led to the hypothesis that U6 snRNA functions as a catalytic element during pre-mRNA splicing. The highly conserved region of U6 snRNA has a structural similarity with the catalytic domain of the negative strand of the satellite RNA of tobacco ring spot virus [(-)sTRSV], suggesting that the highly conserved region of U6 snRNA forms the catalytic center. We examined whether synthetic RNAs consisting of the sequence of the highly conserved region of U6 snRNA or various chimeric RNAs between the U6 region and the catalytic RNA of (-)sTRSV could cleave a substrate RNA that can partially base-pair with them and have a GU sequence. Chimeric RNAs with 70 to 83% sequence identity with the conserved region of S. pombe U6 snRNA cleaved the substrate RNA at the 5' side of the GU sequence, which is shared by the 5' end of an intron in a pre-mRNA. We found that the highly conserved region of U6 snRNA and the catalytic domain of (-)sTRSV are strikingly similar in structure to the catalytic core region of the group I self-splicing intron in cyanobacteria. These results suggest that U6 snRNA, (-)sTRSV and the group I self-splicing intron originated from a common ancestral RNA, and support the hypothesis that U6 snRNA catalyzes pre-mRNA splicing reaction.

Base Sequence↗

Induction of antitumor activities in spleen cells from mice and rats activated with lipopolysaccharide immobilized on beads.

Lipopolysaccharides (LPS) were coupled to polystyrene beads in order to apply the LPS without toxicity. The antitumor activity of the LPS-immobilizing beads was studied in experiments in vitro and in vivo. In vitro studies showed that spleen cells from C3H/HeN mice stimulated by beads immobilizing LPS from Escherichia coli produced cytolytic activity as strong as that of lymphokine-activated killer (LAK) cells. Spleen cells from Sprague-Dawley rats stimulated by beads immobilizing LPS from Salmonella minnesota produced cytolytic activity stronger than that of LAK cells. However, spleen cells stimulated by beads immobilizing each component of the LPS separately could not induce cytolysis. Contact stimulation, even for a brief period, sufficed for cytolytic activity, and was enhanced by culture for 48-72 h. Through in vivo studies, the suppression of tumor growth and a prolongation of the survival time were observed in tumor-bearing mice injected with spleen cells activated by beads immobilizing LPS from E. coli, and in mice injected with LAK cells. The effect of the activated spleen cells was stronger than that of the LAK cells. In rats bearing metastatic tumors, spleen cells activated by beads immobilizing LPS from S. minnesota suppressed lung metastases more strongly than did LAK cells. These findings indicate that LPS immobilized by beads induced killer cells more strongly than interleukin-2. Ex vivo immunomodulation with LPS-immobilizing beads can be applied usefully as an anticancer treatment.

Animals↗

Effect of probucol on recovery from streptozotocin diabetes in rats.

The present study was conducted to see the effect of probucol on streptozotocin diabetes in rats. After 2 weeks of a 1% probucol diet, 35 or 50 mg/kg of streptozotocin were intravenously injected into male Wistar rats. All the rats became diabetic 2 days after treatment. Thereafter, in order to see the effect of probucol on spontaneous recovery from streptozotocin diabetes, 25 mg/kg of streptozotocin was injected into rats after two weeks of probucol diet and the diet was continued for additional two weeks. All the rats with a standard diet (group CS, n = 13) and 12 of 13 rats with probucol diet (group PS) became diabetic 2 days after streptozotocin injection. One rate from group PS did not develop diabetes. Two weeks after injection, only 4 of 13 rats in groups CS showed recovery, while 11 of 12 rats in group PS showed recovery from streptozotocin diabetes (p less than 0.05). The average blood glucose levels in group PS were significantly lower than group CS (10.5 +/- 4.6 vs 18.5 +/- 0.6 mM, p less than 0.05). In addition, the pancreatic insulin content of group PS was 8 times greater than that of group CS (0.75 +/- 0.24 vs 0.09 +/- 0.03 mmol/pancreas, p less than 0.01). Thus, the in vivo diabetogenic action of streptozotocin could not be reduced by pretreatment with probucol. However, recovery from streptozotocin diabetes was induced by subsequent treatment with probucol. The precise mechanisms for this phenomenon were not known; but the present findings suggest the protective effect of probucol on beta-cell damage induced by small dose of streptozotocin.

Animals↗

Efficacy of nafamostat mesilate as a regional anticoagulant in experimental direct hemoperfusion and in plasma exchange on humans.

As an anticoagulant, we compared Nafamostat mesilate (FUT) to heparin in experimental direct hemoperfusion (DHP) and studied the efficacy of FUT in clinical plasma exchange (PE). In in vitro study, FUT (5 micrograms/ml) inhibited the activation of C4 more strongly than heparin (100 U/h), and larger dose of FUT (50 micrograms/ml) inhibited the activation of C3. Experimental DHP with FUT on jaundiced dogs was safely performed, but not with heparin. Clinical PE with FUT was safely performed and the hemostatic condition was not aggravated either during or after PE in patients with bleeding.

Animals↗

On-line cell manipulation for cancer treatment.

We hypothesized that the host immune system is directly stimulated by contact between blood and the materials used in blood purification systems. This concept has never been applied in therapeutic plasmapheresis. Two new materials have been invented since 1983. One of those is lipopolysaccharide (LPS)-immobilized beads, which are chemically bonded bacterial LPS (LPS-B). Another is immobilized pokeweed mitogen (PWM-B). We studied these two materials for their anti-tumor cell activity in vitro and in vivo. Their efficacy on tumor cells was demonstrated to be much stronger than that of lymphocyte activated killer (LAK) cells. Our new concept was proven to be correct.

Animals↗

In vitro monitoring activation by the ligands and specific DNA-binding of the glucocorticoid receptors.

The glucocorticoid receptor is a member of the steroid and thyroid hormone receptor superfamily and acts as a ligand-activated transcription factor. To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits glucocorticoid-induced activation of the latent cytosolic glucocorticoid receptor to an active DNA-binding species. We demonstrate here that cytosol from a rat hepatoma cell, M1.19, contains glucocorticoid receptor-specific immunoreactivities and target DNA-binding activities. Moreover, specific DNA-binding activities of M1.19 cytosol were dose-dependently induced by dexamethasone treatment, and linearly correlated with the hormonal induction of chloramphenicol acetyltransferase activity at the corresponding concentrations. These results indicate that the cytosolic glucocorticoid receptor could be converted in a DNA-binding form under cell-free conditions and the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.

Animals↗

Genomic organization of the human homologue of the rat pancreatic elastase I gene.

The homologue of the rat pancreatic elastase I gene was found in the human genome, but its transcription was completely suppressed in the adult human pancreas as we reported previously. In this study, we characterized the complete structure of the eight putative exons of the silent gene for human elastase I. A genotype analysis of the exon 1 DNA sequence revealed that at least two allelic elastase I genes are present in human genomes. A primate-specific repetitive DNA element (MER1) was identified in the 3'-flanking region of the human elastase I gene. The primary structure of human preproelastase I, deduced from the sequences of the eight exons, showed an 89% identity with that of porcine or rat pancreatic preproelastase I. The amino acid residues of the serine protease catalytic triad and the eight cysteine residues conserved in the elastase family were present at positions equivalent to those observed in porcine and rat elastase I, suggesting that the gene product may function as an elastolytic enzyme if this gene is expressed in any tissue.

Amino Acid Sequence↗