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Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 469 records · Page 26Linked to original sources

Urinary and biliary metabolites of daidzin and daidzein in rats.

Examination was made of the urinary and biliary excretion of metabolites of daidzin and daidzein, the major components of roots of Pueraria lobata Ohwi (Leguminosae) in rats. The urine of rats administered daidzin orally contained four major metabolites, daidzein 7,4'-di-O-sulfate (M-1), daidzein 7-O-beta-D-glucuronide (M-2), daidzein 4'-O-sulfate (M-3), daidzein (M-4), as determined from spectroscopic and chemical data. The urine of rats treated with daidzein contained M-2--M-4 in the above metabolites. Total cumulative amounts of the four metabolites excreted in the urine at 48 h following the oral administration of daidzin and daidzein were approximately 4.8% and 4.6% of the doses administered, respectively. The bile of rats administered daidzin orally contained M-1--M-4. Daidzein 7-O-beta-D-glucuronide 4'-O-sulfate (M-5), a major biliary metabolite, was identified by the high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectra. At least daidzin appeared to be hydrolyzed to aglycone after absorption in the body, and as a part of metabolites, M-1--M-4 having free hydroxyl, glucuronided or sulfated hydroxyls at the C-7 position, may then be excreted in the urine and bile.

Administration, Oral↗

[Determination of synephrine in oriental pharmaceutical decoctions containing evodiae fructus by ion-pair high-performance liquid chromatography].

A simple and precise method was established for the determination of synephrine in oriental pharmaceutical decoctions containing Evodiae Fructus using high-performance liquid chromatography with sodium dodecyl sulfate (SDS) as an ion-pair reagent. Synephrine was eluted within 25 min without interference from co-existing components using an ODS column and a mixture of water-acetonitrile-SDS-phosphoric acid (70:30:0.5:0.1, v/v/w/v) as a mobile phase.

Chromatography, High Pressure Liquid↗

Alteration of ganglioside composition in the erythrocytes associated with Theileria sergenti infection.

The changes in ganglioside composition of bovine erythrocytes associated with Theileria sergenti infection were investigated using the erythrocytes before and after the infection. The erythrocytes before infection with T. sergenti had GM3, sialosylparagloboside (SPG), i-active, and I-active ganglioside as predominant gangliosides. After infection with T. sergenti merozoites, the contents of SPG and i-active ganglioside were slightly less, and I-active ganglioside content was much less in the erythrocytes, though GM3 content did not so vary. The decreased I-active ganglioside content showed a recovery as the parasitemia waned to low level in the infected cattle. The total amount of lipid-bound sialic acid also decreased in the erythrocytes after the infection. Similar changes were also caused by the incubation of liposomes containing ganglioside fraction obtained from bovine erythrocytes with T. sergenti piroplasms. These results suggest that the reduction of the contents of SPG, i-active, and I-active ganglioside on the erythrocytes was related to the T. sergenti infection.

Animals↗

A novel liposome immune lysis assay (LILA) for determination of CRP antigen using two monoclonal antibodies recognizing different antigenic determinants.

We have already developed the liposome immune lysis assay (LILA) for the determination of C-reactive protein (CRP) by employing an inhibition method and a sandwich method. We herein report a new LILA system involving the use of monoclonal antibodies-bearing liposomes. We established five monoclonal antibodies to CRP antigen, AC-1, -2, -3, -4, -5 which had the capacity to activate complement and form antigen-antibody complex. Each of these antibodies was covalently coupled to carboxyfluorescein-entrapped multilamellar liposomes. When the liposomes were incubated with CRP antigen in the presence of guinea pig complement, CRP antigen-dependent liposome lysis was observed but the sensitivity was not great enough for practical use. On the other hand, when liposomes coupling two monoclonal antibodies (AC-1, AC-2) which recognized distinct CRP antigenic determinants were employed in the assay, the sensitivity increased compared with that using only one monoclonal antibody, and the detectable concentration range was 5-300 ng/ml. These results indicated that the combination of two or more monoclonal antibodies which recognize distinct CRP antigenic determinants is effective for increasing the sensitivity of the assay.

Animals↗

Physicochemical damage to liposomal membrane induced by iron- or copper-mediated lipid peroxidation.

A carboxyfluorescein (CF)-enveloping soybean phosphatidylcholine liposome was used as a model of physicochemical damage of biomembranes. The liposomes were exposed to a metal-chelate complex [2 mM of ferric nitrilotriacetate (FeNTA) or cupric nitrilotriacetate (CuNTA)] plus a reductant (2 mM of ascorbate or various concentrations of reduced glutathione), and CF release from damaged liposomal membranes and the generation of thiobarbituric acid-reactive substances (TBARS) were measured. In the presence of a reducing agent, both FeNTA and CuNTA stimulated markedly CF release and an increase in the TBARS level, while in the absence of a reducing agent both of the chelate complexes showed little CF release and TBARS. The effects of H2O2 addition to the reaction system containing liposome with FeNTA or CuNTA plus ascorbate were also examined. The CF release was slightly increased by the addition of a smaller dose (0.5 mM) of H2O2 and it was inhibited by 8 mM of H2O2. A similar result was obtained in the TBARS test. These results suggest that FeNTA- or CuNTA-mediated lipid peroxidation can damage liposomal membranes physicochemically, and the redox reaction of the chelated metal itself is more important than a Fenton-type reaction in the process.

Ferric Compounds↗

Successful delivery in a pregnant women with crescentic IgA nephropathy.

A 27-year-old Japanese female developed nephrotic syndrome and impaired renal function during pregnancy. A renal biopsy performed at 21 weeks of gestation revealed crescentic IgA nephropathy. She was treated with steroid pulse therapy followed by conventional steroid therapy. Although the nephrotic syndrome was persistent, the impaired renal function did not deteriorate after the treatment. A live infant was delivered by cesarean section at 37 weeks of gestation. After the delivery, both the nephrotic syndrome and renal insufficiency improved gradually. The indications for renal biopsy and treatments for active IgA nephropathy during pregnancy are discussed.

Adult↗

Anti-glycolipid antibodies produced by Epstein-Barr virus (EBV)-transformed oligoclonal B cell lines obtained from normal persons and autoimmune disease patients.

Oligoclonal B-lymphoblastoid cell lines (LCL) were blindly established by nonimmunized protocol from natural populations of two normal persons and 8 autoimmune disease patients using Epstein-Barr virus (EBV)-induced transformation. We systematically screened these LCLs on antibodies against a panel of glycolipids using liposome immune lysis assay (LILA). Eventually we found antibodies to 12 out of 15 compounds containing CTH, globoside, Forssman, paragloboside, CPH, sulfatide, NAGM3, NGGM3, i active glycolipid, GM1, GA1 and GA2 in 81 out of 950 LCLs from normal PBL, and antibodies to 2 out of 15 compounds containing sulfatide and CPH were also detected in 11 out of 430 LCLs from autoimmune disease patients. Unexpectedly, the antibody repertoire of LCLs from autoimmune disease patients was impoverished. The possibility of the EBV technique for production of various kinds of human monoclonal antibodies (MAbs) to glycolipid was shown.

Antibodies, Monoclonal↗

Inverse relationship between serum cholinesterase activity and the administration of cyclophosphamide: an index of cyclophosphamide therapy.

To determine whether serum cholinesterase activity can be a monitoring index of cyclophosphamide therapy in patients with steroid-resistant glomerulopathy, we compared the cholinesterase activity of 37 patients who received a combined therapy that included the use of cyclophosphamide, prednisolone, antiplatelet drugs, and anticoagulant drugs, with the cholinesterase activity of 25 patients who received prednisolone therapy that excluded cyclophosphamide from the combined therapy. In the prednisolone and the combined groups, cholinesterase activity declined as shown in the following formula: Y = 371-26.4 x log(X): (r2 = 0.28), Y = 444-147.7 x log(X): (r2 = 0.95), respectively. (Y: cholinesterase activity, X: the day after treatment). In the combined therapy group, the prevalence of adverse reactions following treatment in the subgroup below 200 U/l of cholinesterase activity was significantly greater (P < 0.01) than that in the subgroup above 200 U/l of cholinesterase activity. However, there was no significant difference (P < 0.25) in the prevalence of adverse reactions between the subgroups with more or less than 184 U/l of cholinesterase activity following treatment. These results suggest the importance of not going below 200 U/l of cholinesterase activity after treatment when the normal cholinesterase activity range is between 300 and 760 U/l (e.g. less than 65% of the lowest value of the normal range of other hospitals) in order to eliminate the hazards of cyclophosphamide to the patients with steroid-resistant glomerulopathy.

Adolescent↗

[The corticospinal tract lesion of amyotrophic lateral sclerosis--magnetic resonance imaging of the spinal cord].

Magnetic resonance imaging by gradient echo method demonstrated lesions of the lateral corticospinal tract at cervical cord levels in three ALS patients. Patient 1 was a 43-year-old woman with common form of ALS. She developed right-side predominant pyramidal signs, and right-side predominant prolongation of central motor conduction time. MRI showed hypersignal intensity areas in the dorsal region of the lateral column at the 4th and 5th cervical segments with right-side predominancy. Patient 2 was a 65-year-old man with pseudopolyneurtic form of ALS, who showed lower motor neuron signs without a pyramidal sign. MRI of the 3rd and 4th cervical cord segments demonstrated bilateral hypersignal intensity areas in the dorsal part of the lateral column. Patient 3 was a 62-year-old man with common form of ALS, who showed marked bilateral pyramidal signs with Babinski's sign. MRI of the 5th cervical spinal cord segment demonstrated bilateral hypersignal intensity areas in the dorsolateral column. Thus obtained MR images of the spinal cord corresponded well to the postmortem-confirmed degeneration of the spinal corticospinal tract. MRI of the spinal cord performed by gradient echo method would provide additional information on the upper motor neuron involvement in ALS.

Adult↗

[Double crush syndrome in patients with cervical spondylosis or ossification of posterior longitudinal ligament--a clinicophysiological study].

To clarify the clinical characteristics of double crush syndrome (DCS), we evaluated 207 patients with cervical spondylosis (CS) and 19 with ossification of posterior longitudinal ligament of the cervical spine (OPLL) clinicophysiologically. A diagnosis of DCS was based on the following criteria; 1) radiological evidence of CS or OPLL on X-ray films; 2) definite spinal cord compression on cervical magnetic resonance imaging (MRI); 3) neurological deficits in the upper extremities resulting from CS or OPLL; and 4) clinical and/or electrophysiological evidence of entrapment neuropathies in the upper extremities, namely carpal tunnel syndrome (CaTS), Guyon's tunnel syndrome (GTS), and/or cubital tunnel syndrome (CuTS). Pressure-provocative tests were used to confirm clinical entrapment neuropathies. Nerve conduction velocities were also examined. We found 28 patients with DCS (23 CS, 5 OPLL; 12.8% of all patients). There were 9 patients with clinical and electrophysiological DCS, 5 with clinical DCS, and 14 with electrophysiological DCS. Of the total number of patients with DCS, 21 proved to have CaTS, 4 had CuTS, 1 had GTS, 1 had both CaTS and CuTS, and 1 had both CaTS and GTS. Definite spinal cord compression was seen at C5/6 (23 patients), C4/5 (21), C3/4 (13) and C6/7 (10) on cervical MRI. In the majority of patients, neurological deficits of the upper extremities did not result from a single peripheral nerve lesion. It is well known that a discrepancy between neurological manifestation and neuro-imaging sometimes occurs in CS and OPLL, and circulatory disturbance in the spinal cord has been considered a possible pathogenetic mechanism of the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modulation of tumor immunogenicity of rat glioma cells by s-Myc expression: eradication of rat gliomas in vivo.

The Myc family proteins represented by c-Myc are thought to play a crucial role in cellular proliferation, differentiation, transformation, and apoptosis. In this study, we demonstrated the novel role for a Myc family protein in elicitation of immunogenic phenotypes in tumor cells. Injection of rat 9L or C6 glioma cells, together with the s-myc gene linked to the cytomegalovirus promoter, completely prevented formation of both brain tumors and s.c. tumors derived from the parental glioma cells. However, introduction of the s-myc gene had no inhibitory effect on development of B104-derived neuroblastoma. In addition, unlike the s-myc gene, injection of the c-myc or wild type p53 (wt-p53) gene together with glioma cells did not modulate the tumor immunogenicity and resulted in formation of gliomas in the animals. These findings suggest that s-Myc expression may stimulate the presentation of a tumor antigen common to 9L and C6 cells to T lymphocytes and augment the activity of the host immune system, resulting in prevention of glioma formation in vivo. This success in tumor eradication indicates the possibility of application of the s-myc gene for gene therapy of human brain tumors.

Animals↗

[Adjuvant chemo-endocrine chemotherapy with gastrin antagonist after resection of liver metastasis in colorectal cancer].

This study was designed to determine whether or not chemo-endocrine therapy after the resection of liver metastasis from colorectal cancer would prevent re-recurrence in the liver. Postoperatively, seven patients received proglumide gastrin antagonist (1,200 mg/day) +5'-DFUR (800 mg/day) orally for 2 years. MMC 6-10 mg and ADR 20 mg were infused every two weeks alternately for 1 year via catheter in the common hepatic artery. After median follow-up of 39 months, re-recurrence rate in the remnant liver after hepatic resection was 14% (1/7) for patients with chemo-endocrine therapy and 52% (24/46) for the controls. These results suggest the possibility that chemo-endocrine therapy is effective to prevent re-recurrence of liver metastasis in patients with colorectal cancer.

Administration, Oral↗

[A case of liver metastasis from bile duct cancer effectively treated with hepatic artery infusion chemotherapy].

We performed hepatic artery infusion chemotherapy (HAI) combined with 5-FU-MMC-EPIR for bile duct cancer metastasized to the liver. We report a case for which we obtained PR. The case was a 59-year-old woman, who was diagnosed to have multiple liver metastases with an increase of CEA and LDH after 6 months from absolute curative resection for middle bile duct cancer. The patient was catheterized into the proper hepatic artery through the right femoral artery, and 5-FU 500 mg qw, MMC 4 mg q2w, and EPIR 30 mg q4w were infused via a reservoir. Two months after the treatment was begun, CEA and LDH values became normal. At the same time, PR was obtained and was shown upon CT, which continued for 5 months. After an 8-month period during which the patient was an outpatient at PS-0, multiple bone metastases appeared, and the radiotherapy was combinedly utilized for each lesion. The side effect of this method was decrease of leukocytes and blood platelets, but it disappeared by discontinuing medication. The patient died two years after the first operation, a year and four months from the time HAI was begun. It was possible to continue this treatment with PS 1-2 on an outpatient basis until one month before the patient's death. We concluded that hepatic artery infusion chemotherapy is an effective therapeutic method.

Antineoplastic Combined Chemotherapy Protocols↗

["Wrapping therapy" for hepatocellular carcinomas with collateral feeders].

A new treatment method to intercept collaterals with silicone rubber sheeting, called "wrapping therapy", was used for 18 patients with advanced hepatocellular carcinomas having collateral feeders from other organs surrounding the liver. Chemoembolization in 17 of the 18 patients in whom it had been conducted more than once, had proven ineffective. Obvious collateral feeders (parasitic branches) to the tumors were recognized on hepatic angiograms in two-thirds of the patients. This procedure was followed by regional chemotherapy and/or chemoembolization. The 3- and 4-year survival rates of the patients after "wrapping therapy" were 54% and 54%, respectively. This therapy is worth using for hepatocellular carcinomas uncontrolled by arterial therapy because of development of collateral feeders.

Aged↗

[An extended operation for scirrhous gastric cancer--its significance and procedure].

We have been performing an extended operation for scirrhous gastric cancer, namely left upper abdominal exenteration plus Appleby's method, and compared the prognosis among macroscopic subtype classifications. The surgical procedure of left upper abdominal exenteration plus Appleby's method is to resect the neighboring organs of the stomach in an en bloc fashion. It consists of total gastrectomy, partial pancreatectomy, splenectomy, transverse colectomy, cholecystectomy, resection of the left adrenal gland, and ligation and resection of the common hepatic artery. D4 lymph node dissection is carried out. Extended operations were performed for 45 cases of P0-1 scirrhous gastric cancer in 1983-1990. There were 25, 17 and 3 cases of giant fold type, erosive type and stenotic type scirrhous gastric cancers, respectively. Positive lymph node metastases were found in 64% of giant fold type cases and 82% of erosive type cases. In Po, T3-4 cases, cytology of intraoperative peritoneal lavage was positive in 27% of giant fold type cases and 50% of erosive type cases. Although there were no obvious macroscopic invasions found during the operative procedure, later histological study showed invasion to the left adrenal gland in 14% of giant fold type cases and 0% of erosive type cases, and invasion to the transverse colon in 21% of giant fold type cases and 15% of fold type and erosive type scirrhous gastric cancer according to the histological invasion of transverse colon were 25% in positive cases and 27% in negative cases (p = 0.27), 0% in positive cases and 27% in negative cases (p = 0.27), respectively. In giant fold type scirrhous gastric cancer, the extended operation is favorable. In erosive type scirrhous gastric cancer, peritoneal dissemination is observed with a high incidence. Therefore, prophylactic therapy is significant.

Adenocarcinoma, Scirrhous↗

Comparative thrombolytic properties of tissue-type plasminogen activator and of a plasminogen activator inhibitor-1-resistant glycosylation variant, in a combined arterial and venous thrombosis model in the dog.

rt-PA-K, a variant of recombinant tissue-type plasminogen activator (rt-PA) with substitution of amino acids 296 to 299 with alanine (KHRR296-299AAAA) has increased fibrin-specificity and reduced sensitivity to plasminogen activator inhibitor-1; rt-PA-T, with threonine 103 replaced by asparagine has an additional glycosylation site and a reduced clearance; and rt-PA-N, with asparagine 117 mutagenized to glutamine lacks the high mannose carbohydrate side chain. We have investigated whether combination of these properties in a single molecule might yield an improved thrombolytic agent. The thrombolytic potency and fibrin-specificity of the combination mutant rt-PA-TNK was compared with that of rt-PA in a combined venous whole blood clot model and platelet-rich arterial eversion graft thrombosis model in dogs given intravenous heparin and aspirin. Infusion of 0.125 to 1.0 mg/kg over 60 min in groups of 4 to 5 dogs produced dose-dependent fibrin-specific venous clot lysis. The thrombolytic potency (percent lysis per mg compound administered per kg body weight) of rt-PA-TNK was significantly higher than that of rt-PA as evidenced by a higher maximal rate of lysis of 480 +/- 100% versus 140 +/- 40% within the 2 h observation period per mg of compound administered per kg body weight (mean +/- SEM, p = 0.004) and a significantly lower dose of 0.08 +/- 0.01 versus 0.21 +/- 0.04 mg/kg body weight at which the maximal rate of lysis was obtained (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[123I-MIBG myocardial scintigraphical analysis in patients with and without autonomic disorder].

We investigated cardiac sympathetic nerve abnormalities using 123I-metaiodobenzylguanidine (MIBG) in patients with and without autonomic failure (AF), presenting mainly with orthostatic hypotension. 123I-MIBG myocardial scintigraphy was performed in 7 patients with AF, in 10 patients without AF and in 5 normal subjects. Absence of myocardial damage was confirmed in all of the subjects using 210thallium scintigraphy and ultrasound. All of the patients with AF and 4 without AF showed extremely diminished MIBG uptake. 123I-MIBG myocardial scintigraphy is generally useful for detecting adrenergic nervous system dysfunction. Possible confounding factors such as drugs or myocardial beta-receptor dysfunction should be carefully eliminated in patients without AF, because false-negative uptake of MIBG may be seen in some of them.

3-Iodobenzylguanidine↗