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Biomedical subjects

S Yasuda

Publications and source records attributed to S Yasuda.

At least 217 records · Page 12Linked to original sources

Monocyte-derived cultured dendritic cells are susceptible to human immunodeficiency virus infection and transmit virus to resting T cells in the process of nominal antigen presentation.

The susceptibility of monocyte-derived cultured dendritic cells (DCs) to human immunodeficiency virus (HIV) infection and their role in viral transmission in the immune response were studied in detail. We observed that highly purified cultured DCs were infected with the T-tropic Lai strain of HIV type 1 (HIV-1Lai) via the CD4 receptor, and this was followed by formation of the complete provirus as detected by PCR. HIV mRNAs were transcribed at only low levels, and virus production was undectable; however, the addition of the purified protein derivative antigen of tuberculin and of autologous resting T cells to HIV-1Lai-infected DCs but not to HIV-1Lai-infected macrophages led to massive HIV transmission and production. These data suggest that the interaction of infected DCs with T cells during the normal immune response could play an important role in the activation and expansion of HIV.

Antigen Presentation↗

Purification and properties of two chitinases from Streptomyces sp. J-13-3.

Two chitinases (Chi-A and Chi-B) purified from Streptomyces sp. J-13-3 had the same molecular weights (31,000) and enzymatic properties (optimum pH and temperature of pH 6.0 and 45 degrees C) but had significantly different isoelectric points (3.9 for Chi-A, 3.5 for Chi-B). Chi-A and -B had identical N-terminal amino acid sequences (ADXAAAWNASSVYTGGGSASYNGHN), similar amino acid compositions, and immunological cross-reactivities. A concomitant decrease of Chi-A and increase of Chi-B was observed in their productions during cultivation.

Amino Acid Sequence↗

Intrasyringal hemorrhage of the cervical cord associated with Chiari type I malformation--case report.

A 34-year-old male presented with intrasyringal hemorrhage associated with Chiari type I malformation manifesting as a history of repetitive severe pain around his neck and back and progressive sensory disturbance. Magnetic resonance imaging clearly demonstrated syringomyelia at the cervical region associated with Chiari type I malformation and hemorrhage in the syrinx which was strongly suggestive of bleeding into pre-existing syringomyelia or Gowers' syringal hemorrhage. Irrigation of the syrinx and syringosubarachnoid shunting were performed, but rebleeding occurred causing shunt malfunction. Shunt revision was performed, but a new cavity developed above the original syrinx. Foramen magnum decompression resulted in successful reduction of the new syrinx and subsequent neurological improvement. Simultaneous foramen magnum decompression and syrinx irrigation may be a better approach to treat this disease.

Adult↗

[High tissue concentration of 5-FU reduced local recurrence after administration of tegafur suppositories].

Forty-two patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively and clinical value of this treatment was assessed. In a group which indicated tumor tissue concentrations of 5-FU were more than 0.5 micrograms/g, local recurrence decreased in the period of postoperative observation for 42 months. A survival rate of this group was better than others. From these results, preoperative tegafur suppository treatment seemed to have a role in expectation of improvement of local control in head and neck cancer therapy.

Chemotherapy, Adjuvant↗

[Augmentation by succinylcholine of the neuromuscular blocking effect of vecuronium in children].

To evaluate the influence of succinylcholine (Scc) on the neuromuscular blocking effect of subsequently administered vecuronium in children, 30 patients aged 2-14 years scheduled for elective surgery were studied after obtaining the informed consent from the parents. Anesthesia was induced with inhalation of sevoflurane, nitrous oxide and oxygen. T1 of the adductor pollicis muscle to ulnar nerve stimulation elicited by train of four stimulation at 2 Hz was monitored continuously by an acceleration transducer. The patients were divided into two groups; group V (16 patients) received vecuronium (0.03 mg.kg-1) and group SV (14 patients) received vecuronium (0.03 mg.kg-1) after 100% recovery of twitch from neuromuscular blockade induced with Scc (1.0 mg.kg-1). Short onset of action and potentiation of maximal block were demonstrated in group SV. After vecuronium administration, a complete suppression of T1 was observed in 8 patients of group SV and only 1 patient of group V. The present study demonstrates that the neuromuscular blockade of vecuronium can be potentiated with the prior administration of Scc in pediatric patients.

Adolescent↗

[Dissection-like artifact on one-second scanning time CT].

Dissection-like artifact (DLA) is noted only on one-second scanning time CT image. It is usually observed in the ascending aorta, and less commonly in the superior vena cava and right pulmonary artery. We evaluated 136 cases of thoracic CT (including 20 cases of heart failure), and examined how often and where the artifact is noted and why it is produced. DLA was noted in the ascending aorta in 99 cases. Among the 99 cases, the same artifacts were also shown in the superior vena cava in 26 cases, and in the right pulmonary artery in 10 cases. DLA was never observed in other great vessels, such as the descending aorta and inferior vena cava. This artifact was not demonstrated in patients with heart failure. We presume that DLA is produced by pulsation of the ascending aorta and pulmonary artery. If the artifact is observed, the patient does not have severe cardiac impairment.

Adolescent↗

[Whole mediastinal irradiation with or without entire hemithoracic irradiation for invasive thymoma].

We retrospectively reviewed the case histories of 45 patients with invasive thymoma who underwent postoperative or definitive radiotherapy. Patients in stage II or stage III were classified according to the treatment volume as follows: a) those who received irradiation confined to the primary tumor site with a generous margin (involved field group, n = 17) and b)those who received prophylactic whole mediastinal irradiation with or without entire hemithoracic irradiation (prophylactic group, n = 21). Seven recurrences were observed among the involved field group, while all patients in the prophylactic group were relapse-free and alive after a median follow-up interval of 50 months. Major side effects were observed in two patients who received entire hemithoracic irradiation. One developed severe pneumonitis resulting in lung fibrosis that required hospitalization, while the other developed nephrotic syndrome of unknown cause. We conclude that whole mediastinal irradiation with or without entire hemithoracic irradiation can be used as a treatment of choice for postoperative invasive thymoma.

Adult↗

Determination of a new H(+)-K+ ATPase inhibitor (E3810) and its four metabolites in human plasma by high-performance liquid chromatography.

A method for the simultaneous determination of E3810, 2-[(4-(3-methoxypropoxy)-3-methyl pyridine-2-yl)methyl sulfinyl]-1H-benzimidazole sodium salt and its four metabolites, demethylated-E3810 (DM), demethylated thioether-E3810 (DMTE), sulfone-E3810 (S), and thioether-E3810 (TE), in human plasma by high-performance liquid chromatography (HPLC) with UV absorbance detection has been established. The correlation coefficient for all the standard curves was 0.998 or greater. The quantitation limit was 5 ng/ml for E3810 and 20 ng/ml for each of its four metabolites. The recovery of E3810 and its four metabolites from human plasma was high, being greater than 80% when 100 ng of each substance was added per tube, except for DM (74.1%). The stability of E3810 and its four metabolites was evaluated and the following results were obtained: (1) when samples were centrifuged within 20 min after collection, there was no loss of E3810 or its metabolites; (2) when 100 microliters of a 1% aqueous solution of diethylamine was added within 20 min after plasma isolation, there was no loss of E3810 or its metabolites; and (3) there were no stability problems during storage for a period of 10 months at -20 degrees C.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Incorporation of norleucine at methionine positions in recombinant human macrophage colony stimulating factor (M-CSF, 4-153) expressed in Escherichia coli: structural analysis.

Expression of the 17.5-kDa truncated form of human recombinant macrophage colony stimulating factor (rM-CSF, 4-153) in Escherichia coli is complicated by the replacement of methionine residues by norleucine. In order to detect and quantitate this mistranslational event, the intact and the S-carboxyamidomethylated proteins were analyzed by amino acid analysis, automated Edman amino acid sequencing, and electrospray mass spectrometry. In addition, the endoproteinase Glu-C generated peptides were subjected to amino acid sequencing, high-performance liquid chromatography, and electrospray ionization mass spectrometry. The extent of norleucine substitution in different batches of rM-CSF varied between 0% and 20%. The relative instability of methionine residues needs to be considered when calculating the extent of norleucine substitution at methionine positions. The mass spectrometry of the intact rM-CSF allowed for examination of the distribution of multiply substituted methionine to norleucine species, and it enabled detection and quantitation of the norleucine incorporation down to the approximately 3% level. Selective ion chromatograms of molecular ions of interest obtained in reversed-phase high-performance liquid chromatography/electrospray ionization mass spectrometry of proteolytic fragments offered a reliable and fast method of detection and quantitation of norleucine-containing peptides. Norleucine residues were uniformly distributed among all four methionine positions (10, 27, 61, and 65). A substitution of methionine by its structural norleucine analog does not have any effect on the activity of the refolded rM-CSF dimers.

Amino Acid Sequence↗

Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the superantigen staphylococcal enterotoxin B.

BACKGROUND/AIMS: Staphylococcal enterotoxin B (SEB) acts as a superantigen binding to class II major histocompatibility complex proteins, and this complex stimulates T cells. The aim of this study was to investigate the pathogenic effects of SEB on hepatic injury and lethal shock in mice. METHODS: SEB was administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver injury and levels of circulating cytokines were determined. In vitro cytokine production in response to SEB was also investigated. RESULTS: Intraperitoneal administration of SEB (50 micrograms) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GalN-sensitized mice, with no mortality on injection of up to 100 micrograms SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor alpha (TNF-alpha) levels reached a peak, followed by high levels of serum interferon-gamma (IFN-gamma) up to 10 hours after injection. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody (mAb) protected GalN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-gamma-neutralizing mAb. SEB induced the production of TNF-alpha and IFN-gamma in a dose-dependent manner from splenic mononuclear cells in vitro. CONCLUSIONS: The results show that SEB contributes to lethal shock associated with severe hepatic injury in GalN-sensitized mice and suggest that TNF-alpha and IFN-gamma produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.

Animals↗

Hyposecretion of atrial natriuretic peptide due to associated right atrial infarction in a patient with acute right ventricular infarction?

A patient with acute right ventricular infarction who showed hyposecretion of atrial natriuretic peptide (ANP) in spite of abnormally high right atrial pressure and who died of a severe low cardiac output syndrome is reported. Right atrial infarction, which was proven at autopsy, may be responsible for this endocrine failure.

Atrial Function, Right↗

Coronary reperfusion enhances recovery of atrial natriuretic peptide secretion. Salvaging endocrine function in patients with acute right ventricular infarction.

BACKGROUND: The heart has been demonstrated not only to be a pumping organ but also an endocrine organ secreting atrial natriuretic peptide (ANP). We hypothesized that myocardial ischemia may affect ANP secretion and that reperfusion therapy for acute myocardial infarction can preserve endocrine function of the heart. METHODS AND RESULTS: Twenty patients with acute right ventricular infarction were examined who underwent reperfusion therapy on admission. These patients had proximal occlusion of the dominant right coronary artery involving the right atrial branches: 9 patients with successful reperfusion (SRP group) and the remaining 11 patients with unsuccessful reperfusion (URP group). Within 24 hours after the onset of infarction, a volume loading test was performed after reperfusion therapy with measurements for plasma ANP levels and hemodynamics. Before the volume loading test, the plasma ANP level and mean right atrial pressure were similar between these two groups. However, in the URP group, percent increase in ANP in response to volume loading was strikingly smaller (URP, 45 +/- 18% versus SRP, 133 +/- 25%; P < .01) despite similar percent increase in mean right atrial pressure (URP, 100 +/- 46% versus SRP, 86 +/- 23%). The peak ANP level occurred significantly later in the URP group (69 +/- 16 hours) than in the SRP group (28 +/- 9 hours, P < .001) after the onset of infarction. CONCLUSIONS: The response of ANP release to volume loading is attenuated in patients with right ventricular infarction without coronary reperfusion. However, successful reperfusion induces a rapid recovery of cardiac endocrine function as well as its mechanical function. A sufficiently elevated plasma ANP level may be a useful predictor of hemodynamic improvement in patients with right ventricular infarction.

Aged↗

Amphoteric drugs. I. Synthesis and antiallergic activity of [4-(diphenylmethoxy)piperidino]-, [4-(diphenylmethyl)piperazinyl]- and [4-(diphenylmethylene)piperidino]alkanoic acid derivatives.

A simple method of transforming classical antihistaminics into nonsedative antiallergic agents with strong effects in rat models is described. Various [4-(diphenylmethoxy)piperidino]- (series A), [4-(diphenylmethyl)piperazinyl]-(series B) and [4-(diphenylmethylene)piperidino]alkanoic acid derivatives (series C) were synthesized and examined for antiallergic activities and effects on the central nervous system (CNS), in comparison with the corresponding N-methyl derivatives (1a--c). N-Alkylcarboxylic acids (5a--c) showed stronger inhibitory effects on compound 48/80-induced lethality in rats than the corresponding N-methyl derivatives (1a--c). In particular, N-alkylcarboxylic acids (5a) in series A exhibited approximately 100-fold stronger inhibitory effects than 1a, and were the least effective in prolonging the sleeping time on hexobarbital-induced anesthesia in mice in all series. As a result of chemical modification in series A, it was found that introduction of a methyl group at the para-position on one benzene ring in the (diphenylmethoxy)piperidine system effectively reduced CNS side-effects without reducing antiallergic activity. (+)-3-[4-[(4-Methylphenyl)phenylmethoxy]piperidino]propionic acid ((+)-5l), an optically active isomer of 5l, exhibited a stronger antiallergic effect (ED50 = 0.17 mg/kg, p.o.) than ketotifen and terfenadine in the 48 h homologous passive cutaneous anaphylaxis (PCA) test, and moreover exhibited no CNS side-effects, such as prolongation of the sleeping time on hexobarbital-induced anesthesia, at an oral dose of 30 mg/kg. Compound (+)-5l was thus proved to be a promising candidate as a nonsedative antiallergic agent.

Animals↗

[Establishment and characterization of strain KE-39 derived from human gastric cancer].

We succeeded in establishing a human gastric carcinoma cell line (KE-39) from oncocytes obtained from the primary focus of a 77-year-old male stomach cancer patient. From a histopathological point of view the gastric carcinoma was a poorly differentiated adenocarcinoma exhibiting a funicular from and a structure with a solid vesicular focus. The oncocytes adhered to glass and proliferated in cell clusters, with a doubling time of about 38.4 hours. Upon transplantation of the cancer cells into nude mice, no visible tumors were found, but from a histological point of view poorly differentiated adenocarcinoma similar to the primary focus was found in all cases. With immunological staining they were found to be positive for anti-CEA antibody and anti-CA19-9 antibody, but negative for anti-ICAM-1 antibody. KE-39 is a cell line which was established from the primary focus, and it was reported in the belief that it is a useful cell line, upon the investigation of its cancer metastasis mechanism and cytological characteristics.

Adenocarcinoma↗

Inhibitory effect of simultaneous intraportal administration of 5-fluorouracil, uracil and degradable starch microspheres on experimental hepatic micrometastasis, is of colon cancer.

This study was designed to examine the optimal regimen of 5-fluorouracil (5-FU), uracil and degradable starch microspheres (DSM) to prevent the hepatic metastasis of colorectal cancer. BALB/C mice were used as a model of hepatic micrometastasis of mouse transplantable colorectal cancer, Colon 26. We intraportally administered to the mice 5-FU at a dose of 34.8 mg/kg body weight; uracil at the dose equal to, or 8 times higher than that of 5-FU in molar weight and DMS at a dose of 5 mg/kg body weight. We investigated the hepatic and serum concentrations of 5-FU and uracil and the inhibitory effect of various combinations of the three substances on hepatic metastasis. The study showed that concurrent use of 5-FU with uracil at a dose 8 times higher than that of 5-Fu could keep 5-FU concentration high in hepatic tissue and relatively low in serum. This tendency became more marked with the presence of DSM. These findings support the previous study results that uracil antagonizes breakdown of 5-FU in the liver and with the aid of DSM, retards excretion of 5-FU from the liver. Further investigations for clinical application of this method will lower the incidence of hepatic metastasis of colorectal cancer.

Animals↗

Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers.

E3810 is a new H+,K(+)-ATPase inhibitor with a substituted benzimidazole, which is under clinical investigation for peptic ulcer treatment in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E3810 after oral administration to healthy male subjects. E3810 was administered as: single oral doses (1, 3, 10, 20, 40 and 80 mg) in fasting conditions, a single oral dose (20 mg) after a meal and repeated oral doses (20 and 40 mg) once daily for 7 days. The concentrations of E3810 and its metabolites in plasma and urine were determined by HPLC methods with UV detection. E3810 was generally well tolerated by all subjects. In the single-dose study, Cmax and AUC increased with increasing doses in the dose range examined. The mean plasma half-life was about 1.0 hour and was dose-independent. The apparent oral clearance of E3810 ranged from 4.37 to 8.40 ml/min/kg. No significant deviation from linear pharmacokinetics was observed. Approximately, 30% of a dose was excreted into the urine as thioether carboxylic acid-E3810 and its glucuronide. The mean serum protein binding was 96.3%. No effect of food intake on the Cmax and AUC was observed while tmax after a meal was 1.7 hours longer than that in the fasting conditions. No appreciable change in drug pharmacokinetics was observed during repeated oral dosing of E3810.

2-Pyridinylmethylsulfinylbenzimidazoles↗