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Biomedical subjects

E Suzuki

Publications and source records attributed to E Suzuki.

At least 217 records · Page 12Linked to original sources

Theoretical relationship between the post-administration time and plasma or urinary concentration of a metabolite and the unchanged drug. Administration of caffeine to horses.

In a doping test for racing horses, it is useful for the elucidation of the illegal use of drugs if one can estimate the time at which the detected drug was administered. In order to estimate the time which has elapsed after the administration of caffeine (CA) into horses, the ratios of concentration for the respective metabolites to the unchanged CA in the plasma or the urine were determined. These ratios have been known to be independent of the dose of CA. The relationship between [plasma or urinary concentration of a metabolite]/ [plasma or urinary concentration of the unchanged drug] and the post-administration time of CA was expressed in a theoretical equation using pharmacokinetic parameters. When CA was administered at 2.5 mg/kg intravenously, intramuscularly or orally, all of the experimentally observed values of plasma or urinary metabolites: theophylline, theobromine and paraxantine, agreed well with the theoretical formulas, indicating that there exists a theoretical relationship between the post-administration time and the concentration ratio of the respective metabolites to unchanged CA.

Animals↗

Preparation of specific antiserum to 17 alpha-estradiol 17-N-acetylglucosaminide.

A specific enzyme immunoassay (EIA) method has been developed for 17 alpha-estradiol 17-N-acetylglucosaminide as a model compound instead of 15 alpha-hydroxyestrogen 15-N-acetylglucosaminides. Two new haptens, 3-(omega-carboxyalkyl) ether derivatives of 17-alpha-estradiol 17-N-acetylglucosaminide, were synthesized and conjugated with bovine serum albumin (BSA). The EIA was newly established using specific antiserum elicited against 3-(1-carboxypropyl) ether of 17 alpha-estradiol 17-N-acetylglucosaminide (17NAG CPE)-BSA conjugate and beta-galactosidase-labeled 17NAG CPE as a labeled antigen. An appropriate dose-response curve of EIA for 17 alpha-estradiol 17-N-acetylglucosaminide was obtained in the range of 20-1000 pg/tube. The specificity of EIA proved to be satisfactory in terms of cross-reactivities to related compounds including 15 alpha-N-acetylglucosaminides. The proposed method will be applicable to the preparation of antisera for use in EIA of 15 alpha-hydroxyestrogen 15-N-acetylglucosaminides.

Acetylglucosamine↗

Dose-dependent gastrointestinal absorption of 5-fluorouracil in rats in vivo.

Dose-dependent gastrointestinal absorption of 5-fluorouracil (5-FU) was kinetically evaluated in rats in vivo by analyzing gastrointestinal disposition after oral administration, where a linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction versus time profiles for the stomach and small intestine to estimate the rate constants of gastric emptying (kg) and intestinal absorption (Ka). With an increase in dose from 1.5 nmol/rat (low dow) to 15 mumol/rat (high dose), the Ka decreased from 5.95 to 0.55 min-1, suggesting the involvement of carrier-mediated transport. This study is the first to demonstrate the dose-dependent gastrointestinal absorption of 5-FU in vivo, though it has long been suggested in situ and in vitro. Meanwhile, at both the low and high doses, the Kg values, which were unaffected by dose (0.069 and 0.082 min-1, respectively, for the low and high doses), were smaller than the Ka values by an order of magnitude or more and the recovery of 5-FU was negligible, compared with that of inulin (a nonabsorbable marker), in the most distal segment of ileum. These results suggest that, regardless of dose, 5-FU is highly absorbable in a gastric emptying-limited manner. Thus, well-publicized bioavailability problems (low and erratic) of 5-FU may be attributable to extensive and variable first-pass metabolism rather than poor and variable gastrointestinal absorption.

Animals↗

Method of obtaining mutants defective in immunoglobulin mu transcription factors.

A method of obtaining mutants defective in the regulatory function of Ig mu gene expression was developed. Such mutants are useful for discovering the functions of transcription factors and isolating their genes, especially those of DNA-unbinding factors. Cells expressing Ig mu and Eco-GPT simultaneously under control of each mu enhancer were prepared as follows: myeloma X63Ag8.653 cells were transfected with pSV-V mu Me delta CH1 encoding a mu gene modified for cell surface mu expression without light chains, selected by neomycin resistance, transfected with Eco-GPT gene connected to the mu enhancer, and selected with mycophenolic acid in a medium containing xanthine. The mu(m)/Eco-GPT cells were mutated with ethane methyl sulfonate (EMS), and selected with toxin-conjugated anti-mu antibody, and then with 6-thioguanine. The mu(M)-/Eco-GPT- mutants obtained were fused with X63Ag8.653 cells. Fusion caused the mutant to recover mu(M) expression, suggesting that some trans-acting transcription factor other than the mu-encoding gene itself was probably mutated.

3T3 Cells↗

Subacute thyroiditis with thyroid-stimulation blocking antibodies: a case report.

A 43-year-old female showing signs and symptoms of subacute thyroiditis was referred to our hospital for further evaluation of her thyroid function because TSH-binding inhibitor immunoglobulins (TBII) were detected in her serum. A diagnosis of subacute thyroiditis was made based on high levels of thyroid hormones with suppressed TSH level, suppressed radioactive iodine uptake (RAIU), and positive inflammatory findings and ultrasonogram results. She was at first thyrotoxic, then transiently hypothyroid, and finally became euthyroid. The assay results for TBII and thyroid-stimulation blocking antibodies (TSBAb) were positive in the thyrotoxic phase, and the TBII and TSBAb activities were decreased and finally became undetectable during the course of her illness. In contrast, the assay results for thyroid-stimulating antibodies (TSAb) were negative throughout the investigation period. The presence of TSBAb may have induced the development of hypothyroidism because she became euthyroid after the disappearance of TSBAb from the serum, but the duration of the hypothyroid phase was the same as that in typical cases of subacute thyroiditis. Inflammatory or destructive changes in the thyroid gland are thought to be involved in the production of the TSH-receptor antibodies in the patient.

Adrenergic beta-Antagonists↗

Expression of a bifunctional chimeric protein A-Vargula hilgendorfii luciferase in mammalian cells.

We have designed and constructed a novel chimeric protein that consisted of a single domain of protein A and luciferase derived from sea-firefly Vargula hilgendorfii with the goal of obtaining a heterofunctional immunological tool. The structural gene of luciferase was fused to the 3' terminus of the D domain gene of protein A with/without a short linker of five amino acids. The resulting constructs under the transcriptional regulation of the Rous sarcoma virus (RSV) promoter, were expressed transiently in simian COS-1 and stably in Chinese hamster ovary (CHO) cells. The properties of the resultant chimeric protein were characterized. The results indicated that the dual properties of the chimeric protein could be retained only after the introduction of a linker of (Gly)4 Ser between the two conjugated moieties. Moreover, the chimeric protein was found to retain at least 50% of the specific activity as compared with the non-fused luciferase. The future prospect of the usage of this chimeric protein in the field of diagnostics was further evaluated by performing bioluminescent immunoassays.

Amino Acid Sequence↗

A novel aspect of the maturational step of megakaryocytes in thrombopoiesis: bundle formation of microtubules in megakaryocytes.

We demonstrated bundle formation of microtubules both in the cytoplasmic processes and in the cytoplasm near the nucleus of cultured megakaryocytes by means of electron and immunofluorescent microscopy. To determine whether this bundle formation was related to megakaryocyte maturation, we studied the effects of recombinant human interleukin-6 (rhIL-6) in vitro and in vivo on this event. About 75% of the megakaryocytes in the bone marrow had no fibrous microtubule structures in the cytoplasm (type I), and about 25% had bundles of microtubules (type II). The formation of these bundles was promoted by rhIL-6 both in vitro and in vivo. Considerably more megakaryocytes cultured with recombinant murine (rm) IL-3 and rhIL-6 became type II than those cultured with rmIL-3 alone. Megakaryocytes from mice given rhIL-6 (10 microg/animal/d) subcutaneously also began to form bundles in proportion to an increase in platelet counts. After the administration of rhIL-6, about half of the megakaryocytes contained microtubule bundles in their cytoplasm. These results indicate that microtubule-bundle formation is one maturational event in megakaryocyte development and that rhIL-6 could accelerate this event.

Animals↗

[Hard metal lung with diffuse small nodular shadows].

A 32-year-old woman was admitted to Niigata University Hospital with dyspnea and a non-productive cough. She had been exposed to hard metal dust for 4 years in a metal-polishing factory. Chest X-ray and CT films showed diffuse small nodular shadows in both lung fields and pulmonary-function tests revealed severe restrictive impairment. Specimens obtained by thoracoscopic lung biopsy showed fibrosis in the centers of lobules and in peribronchiolar regions. Giant-cell interstitial pneumonia-like findings were also noted. Tungsten carbide and cobalt were detected in these specimens, with an X-ray microanalyzer. Hard metal lung was diagnosed. By 1 year after she changed her place of work and began corticosteroid treatment her symptoms and pulmonary function had improved remarkably, although shadows on chest X-ray films remained to some extent.

Adult↗

[Three-dimensional images of the cystic duct obtained with helical DIC CT].

Before laparoscopic cholecystectomy, it is important to clarify the anatomy of the cystic duct. This study assessed three-dimensional CT images (3D images) of the cystic duct obtained non-invasively using helical DIC CT and these images were compared with those obtained with ERCP and DIC. The three-dimensional technique using Helical DIC-CT was applied in 168 patients for laparoscopic cholecystectomy. The cystic duct detected by 3D imaging was evaluated for patency, length and bifurcation. Three-dimensional images showed the cystic duct in 157 of 168 cases (93.5%) and in 81 of 89 cases (91%) in which the cystic duct was not clearly visualized on DIC. Among the 23 cases in which were both 3D images and ERCP undergone, 3D images were equal to those of ERCP in detection of the cystic duct in 20 cases, superior to ERCP in two cases, and inferior to ERCP in one. The technique of 3D images proved useful in demonstrating the patency, length and variations in bifurcation of the cystic duct for surgeons performing laparoscopic cholecystectomy and might be substitute ERCP in preoperative assessment.

Cholangiopancreatography, Endoscopic Retrograde↗

Solution structure of an ATP-binding RNA aptamer reveals a novel fold.

In vitro selection has been used to isolate several RNA aptamers that bind specifically to biological cofactors. A well-characterized example in the ATP-binding RNA aptamer family, which contains a conserved 11-base loop opposite a bulged G and flanked by regions of double-stranded RNA. The nucleotides in the consensus sequence provide a binding pocket for ATP (or AMP), which binds with a Kd in the micromolar range. Here we present the three-dimensional solution structure of a 36-nucleotide ATP-binding RNA aptamer complexed with AMP, determined from NMR-derived distance and dihedral angle restraints. The conserved loop and bulged G form a novel compact, folded structure around the AMP. The backbone tracing of the loop nucleotides can be described by a Greek zeta (zeta). Consecutive loop nucleotides G, A, A form a U-turn at the bottom of the zeta, and interact with the AMP to form a structure similar to a GNRA tetraloop, with AMP standing in for the final A. Two asymmetric G. G base pairs close the stems flanking the internal loop. Mutated aptamers support the existence of the tertiary interactions within the consensus nucleotides and with the AMP found in the calculated structures.

Adenosine Monophosphate↗

[Pneumonia due to the Chinese medicine pien tze huang].

A 47-year-old woman who had been treated for chronic hepatitis was admitted to our hospital because of a productive cough that developed after she took Pien Tze Huang. A chest X-ray film revealed a reticular shadow in both lower lung fields and pulmonary-function tests showed a restrictive pattern. Pien Tze Huang was discontinued and the patients condition was observed. No other treatment was given, and the patient's symptoms, laboratory data, chest roentgenographic findings, and pulmonary function gradually improved. The result of a leukocyte migration inhibition test was positive for Pien Tze Huang, and the final diagnosis was drug-induced pneumonia due to Pien Tze Huang. We know of no previous report of Pien Tze Huang-induced pneumonia.

Cell Migration Inhibition↗

[Autoantibodies in bronchial asthma].

We studied the difference in the prevalence of autoantibodies between the sera of atopic asthma and non-atopic asthma. The presence of antinuclear antibodies (ANA) was evaluated in the sera of 20 patients with atopic asthma, 15 with non-atopic asthma, 20 with lung cancer, and 103 control subjects (40 with other pulmonary diseases and 63 with other medical diseases), by using an indirect immunofluorescent assay with HEp-2 cells as a substrate. The incidence of positive ANA was in the sera of 4/20 patients with atopic asthma, 8/15 with non-atopic asthma, 6/20 with lung cancer and 12/103 with control subjects, respectively. The incidence of positive ANA was found to be significantly higher in non-atopic asthma than in atopic asthma regardless of age or sex. One hypothesis is as follows. In non-atopic asthma, viral airway infection, as well as chronic eosinophilic inflammation of the airways, may cause some trouble in the impaired lymphocyte surveillance and may be especially liable to develop autoantibodies under those circumstances.

Adult↗

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

Adult↗

[Central alveolar hypoventilation syndrome with compression of the medulla oblongata by tortuous and elongated vertebral arteries].

A 43-year-old woman was admitted to the hospital with hypoventilation, which developed when she took sedatives because of an operation on an adrenal gland tumor. Central alveolar hypoventilation syndrome was diagnosed after neurophysiological and pulmonary-function tests. Magnetic resonance imaging and vertebral angiography revealed that tortuous and elongated vertebral arteries compressed the ventral sides of the medulla oblongata, which may have caused the hypoventilation. Mechanical ventilation during sleep improved her condition. Home mechanical ventilation was prescribed and she has been well during follow up as an outpatient.

Adult↗

[Recovery from descending necrotizing mediastinitis and multiple organic failure after seven months of mechanical ventilation].

A 61-year-old man with a history of hypertension and diabetes mellitus had a tooth extracted. Nine days later, he was admitted to the hospital with complaints of high fever, dyspnea, and anterior chest pain. Physical examination revealed a drowsy man with a fever of 38.2 degrees C, blood pressure of 66/44 mmHg, and marked redness and swelling from the neck to anterior part of the chest. Laboratory examination indicated severe infection and multiple organ failure, consisting of cardiac, respiratory, renal, and hepatic failure, with disseminated intravascular coagulation. Chest X-ray and CT-scan films showed abscesses extending from the neck to the mediastinum, and bilateral pleural effusion. Immediately, he was treated with catecholamines, furosemide, mechanical ventilation with a high concentration of oxygen, continuous drainage, repeated skin incisions, and broad-spectrum antibiotics. In addition, steroid pulse therapy was administered for persistent respiratory failure. On the 28th hospital day, a fistula developed between the trachea and the mediastinum, and an intratracheal tube had to be inserted through the fistula. On the 212 th hospital day, after intravenous hyperalimentation, continuous intravenous insulin infusion, and administration of broad-spectrum antibiotics, catecholamines, and furosemide, the patient was weaned from mechanical ventilation. A restrictive ventilatory defect due to ankylosis and atrophy of underused muscles was noted after weaning, but the PaO2 was high with a low dose of oxygen (1 to 2 l/min), and 21 months later, the blood gases were normal while the patient was breathing room air. As of January, 1996, he was undergoing rehabilitation to promote his recovery from ankylosis, muscle atrophy, and speech dysfunction.

Catecholamines↗

Isolation and possible composition of glucosylceramides from Paracoccidioides brasiliensis.

Twelve different species of neutral monohexosyl ceramides (CMHs) and two species of neutral monohexosyl ceramides were isolated from mycelium and yeast forms of Paracoccidioides brasiliensis, respectively, by a combination of ion-exchange chromatography, HPLC, and HPTLC. The glucosylceramides did not react with sera from patients with paracoccidioidomycosis (PCM). Carbohydrate analysis indicated that CMHs contain glucose. Analysis of 1H-NMR and mass spectrometry data suggest that the structure of the CMHs is Glcp beta 1-->Cer (mycelium forms present 12 different ceramides and yeast forms present 2 different ceramides). The composition of the lipid moieties was analyzed by negative fast atom bombardment mass spectrometry. No glycosphingolipid other than glucosylceramide was detected in P. brasiliensis.

Animals↗

Control by phosphatidylglycerol of expression of the flhD gene in Escherichia coli.

We reported elsewhere that mutation in the pgsA gene, responsible for the synthesis of phosphatidylglycerol, repressed the synthesis of flagellin and caused the loss of motility of Escherichia coli (Tomura et al., FEBS Letters 329, 287-290, 1993). We now describe evidence for a decrease in promoter activity of the flhD gene, a master gene for flagellum synthesis, in the pgsA3 mutant. We constructed a plasmid with a promoter region of the flhD gene connected with the structure region of the lacZ gene. The activity of beta-galactosidase in the extract prepared from the pgsA3 mutant harboring the fusion plasmid was 30% of that in the wild type cells. This result means that phosphatidylglycerol is likely to be required for the initiation of transcription of the flhD gene. We also found that the motility-less phenotype of the mutant was partially suppressed by elevating incubation temperature. This suppression is caused by restoration of transcription of the flhD gene by high temperature. As the content of phosphatidylglycerol did not increase by elevating incubation temperature, we proposed that this suppression is caused by alternation of a physical structure of phospholipid bilayers in cytoplasmic membranes.

DNA-Binding Proteins↗

Schizophrenic patients with deficit syndrome have higher plasma homovanillic acid concentrations and ventricular enlargement.

In order to investigate the biological characteristics of deficit syndrome in schizophrenia (Carpenter et al 1988), we examined cerebroventricular ratios (CVRs) and plasma concentrations of homovanillic acid (HVA) in a group of schizophrenic inpatients with deficit syndrome (n = 20) and in a control group of age- and sex-matched schizophrenic inpatients without deficit syndrome (n = 20). Symptoms and intelligence levels were measured using the Brief Psychiatric Rating Scale (BPRS) and the Wechsler Adult Intelligence Scale (WAIS), respectively. Patients in the deficit group had significantly higher CVRs as well as significantly elevated plasma HVA concentrations when compared with patients in the nondeficit group. We also found that the mean total WAIS score in the deficit group was significantly lower than that in the nondeficit group. These findings suggest the biological heterogeneity of schizophrenia. Increased central dopaminergic turnover, as indicated by higher plasma HVA concentrations, may partially account for the pathogenesis of deficit syndrome.

Adult↗