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Biomedical subjects

Y Asano

Publications and source records attributed to Y Asano.

At least 595 records · Page 33Linked to original sources

Modulation of immune response against tumor cells by the in vivo administration of an autoreactive Th clone.

The immunization of C3H mice with irradiated syngeneic MM48 tumor cells induced specific tumor-neutralizing cells (TNC). The TNC activity was mediated by the L3T4+, Ly-2- T cell population, and the generation of TNC coincided with the appearance of delayed-type hypersensitivity response against MM48 antigen. The administration of an auto-I-Ak reactive T helper cell clone MS202 to normal C3H mice resulted in the facilitation of growth of MM48 tumor due to the induction of T suppressor (Ts) cells. Splenic T cells from animals given this T cell clone inhibited the TNC activity of immunized mice resulting in the escape of MM48 from the TNC effect. The surface phenotype of the Ts cells was L3T4+, Ly-2-. The Ts cells induced by the clone MS202 were totally antigen-nonspecific, and were able to suppress both the effector and inductive processes of TNC. The results suggest the presence of a physiological MHC-restricted T cell circuit that regulates immune responses against the growing tumors.

Animals↗

Henoch-Schönlein purpura after measles immunization.

A three-year-old boy developed Henoch-Schönlein purpura after measles immunization. To our knowledge Henoch-Schönlein purpura in this setting has not been previously reported. This case illustrates that measles vaccine can act as an inducing factor Henoch-Schönlein purpura.

Antibodies, Viral↗

A new NAD+-dependent opine dehydrogenase from Arthrobacter sp. strain 1C.

A new NAD+-dependent opine dehydrogenase was purified to homogeneity from Arthrobacter sp. strain 1C isolated from soil by an enrichment culture technique. The enzyme has a molecular weight of about 70,000 and consists of two identical subunits with molecular weights of about 36,000. The enzyme catalyzed a reversible oxidation-reduction reaction of opine-type secondary amine dicarboxylic acids. In the oxidative deamination reaction, the enzyme was active toward unusual opines, such as N-[1-R-(carboxyl)ethyl]-S-methionine and N-[1-R-(carboxyl)ethyl]-S-phenylalanine. In the reductive secondary amine-forming reaction with NADH as a cofactor, the enzyme utilized L-amino acids such as L-methionine, L-isoleucine, L-valine, L-phenylalanine, L-leucine, L-alanine, and L-threonine as amino donors and alpha-keto acids such as pyruvate, oxaloacetate, glyoxylate, and alpha-ketobutyrate as amino acceptors. The product enzymatically synthesized from L-phenylalanine and pyruvate in the presence of NADH was identified as N-[1-R-(carboxyl)ethyl]-S-phenylalanine.

Amino Acids, Dicarboxylic↗

Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I.

The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in humans. The malignant transformation occurs after a long latency in some carriers, and its mechanism appears to be distinct from that of other classes of retroviruses which induce transformation through viral or cellular oncogenes. A widely postulated explanation is that the products of novel pX genes transactivate endogenous cellular genes which lead to tumor development in T cells. To directly examine the pathological effects of pX genes in vivo, we produced transgenic mice harboring the HTLV type I pX genes under several regulatory units: HTLV type I long terminal repeat, immunoglobulin enhancer-simian virus 40 promoter, and mouse mammary tumor virus long terminal repeat. Atrophy of the thymus was characteristic in these mice no matter which regulatory unit directed the expression of the genes.

Animals↗

Cardiac arrhythmias in hemodialysis patients. A study of incidence and contributory factors.

Cardiac arrhythmias were evaluated in 100 patients undergoing regular maintenance hemodialysis for chronic renal failure by Holter ECG monitoring a 72-hour period beginning on the day of hemodialysis. Clinically significant ventricular arrhythmias (more than 700 beats/24 h) were found in 18 patients (the frequent group) in whom premature ventricular contractions (PVCs) were recorded frequently during and for 4 h after hemodialysis. In the frequent group, the values of the serum calcium concentration times those of phosphorus were significantly higher than those of patients without PVCs (the no arrhythmia group) or those with fewer PVCs (less than 700 beats/day; sporadic group) (54.9 +/- 3.5 vs. 43.8 +/- 3.2, 43.0 +/- 1.8, respectively; p less than 0.005). Also, in the frequent group, the percent fractional shortening of the left ventricle, as measured by two-dimensional echocardiography, was significantly lower than those in the no arrhythmia and sporadic groups (30.7 +/- 1.8% vs. 40.7 +/- 1.9%, 37.7 +/- 1.1%, respectively; p less than 0.01). On the other hand, in those with frequent premature atrial contractions, the left atrial end-diastolic dimension was significantly enlarged (42.1 +/- 1.2 mm vs. 36.5 +/- 1.1 mm, 38.1 +/- 0.9 mm, respectively; p less than 0.01). From these results, we conclude that impaired cardiac performance and a high calcium phosphate product predialysis may be correlated with an increased incidence of ventricular arrhythmias in uremic patients.

Adult↗

Development of drug resistance in cultured clonogenic leukemic blast cells during the clinical course of myeloblastic leukemia.

We studied changes in the drug sensitivity of clonogenic leukemic blast cells from patients with acute myeloblastic leukemia during clinical courses. These cells were assayed using the colony formation technique in methylcellulose culture. Various doses of each of two chemotherapeutic agents, daunorubicin and aclarubicin, were added at the start of culture, and drug sensitivities were measured in terms of percentage inhibition of leukemic blast colony formation. Clonogenic leukemic blast cells became less sensitive to the drugs which were administered to the patients during the course of the disease, suggesting that development of drug resistance in vivo may reflect the presence of dominant resistant populations of clonogenic leukemic blast cells in vitro.

Aclarubicin↗

The role of endogenous dopamine in congestive heart failure.

Although the effects of epinephrine and norepinephrine in congestive heart failure have been extensively studied, and exogenous dopamine, another of the catecholamines, has been widely used for the treatment of congestive heart failure, little attention has been paid to the physiological significance of endogenous dopamine in this condition. The present study was therefore designed to assess the physiological significance of endogenous dopamine in congestive heart failure. Nineteen patients with congestive heart failure caused by such conditions as acute myocardial infarction, valvular disease and dilated cardiomyopathy were examined before and after treatment with diuretics, digitalis and vasodilators. Electrolyte, creatinine and catecholamine concentrations in plasma and urine were analyzed. Urinary dopamine levels were increased in 13 out of 19 cases before treatment and returned to the normal range after treatment, falling from 2448 +/- 950.7 to 528.8 +/- 56.3 micrograms/day (normal level, less than 700 micrograms/day). Urinary dopamine excretion was markedly elevated within 24 hours after the onset of symptoms of heart failure, such as chest pain, palpitations and dyspnea. The relationship between urinary dopamine excretion and time after the onset of symptoms showed a strong statistical correlation (r = 0.55, p less than 0.001). Urinary dopamine excretion was also well correlated with plasma dopamine concentration, urinary norepinephrine excretion and venous pressure. From these results, it is concluded that endogenous dopamine seems to play an important role during the acute phase of congestive heart failure.

Adult↗

Dual regulatory mechanisms of proton transport in rat papillary collecting duct cells in culture.

The regulation of proton transport and cytosolic pH was studied in rat papillary collecting duct (PCD) cells in culture using a pH-sensitive fluorescence probe, 2,7-bis-carboxyethyl-5,6-carboxyfluorescein (BCECF). Data were obtained from confluent monolayers grown on glass coverslips and dipped in a HCO3- -free medium, pH 7.40. The resting intracellular pH (pHi) was 7.16 +/- 0.03 (n = 20). When PCD cells had been acidified by pretreatment with NH4Cl, pHi immediately recovered toward the resting value. Two mechanisms participated in this recovery: a Na+-dependent mechanism which could be inhibited by amiloride (indicative of Na+-H+ exchanger) and a Na+-independent process (a proton ATPase). The pHi recovery from acid loading was inhibited by amiloride to about 55% of the control recovery (half-maximal effect at 100 microM). The rate of pHi recovery after the readdition of Na+ to a sodium-free medium exhibited saturation kinetics (half maximal rate at 28 mM). Dicyclohexylcarbodiimide (DCCD), an inhibitor of a plasma membrane proton ATPase, and the depletion of cellular ATP induced by 2 mM potassium cyanide (KCN) also partially inhibited the rate of pHi recovery after cell acidification with a NH4Cl load. When PCD cells were treated with 1 mM DCCD, amiloride almost completely inhibited pHi recovery. Amiloride and the removal of external Na+ had induced a gradual fall in pHi to a new resting value and rapidly recovered when Na+ was added. We conclude that PCD cells grown in culture have at least two proton transport mechanisms: a Na+-H+ exchanger and a plasma membrane proton ATPase. The kinetics of these processes can be reliably assessed by the pH-sensitive fluorescent probe, BCECF. Both the Na+-H+ exchanger and the plasma membrane proton ATPase may contribute to urinary acidification.

Adenosine Triphosphatases↗

I-J and mechanism of immunosuppression.

I-J has been found to be an inducible isomorphic molecule expressed on class II-restricted T cells. It undergoes a systematic adaptive change in radiation bone marrow chimeras according to the environmental major histocompatibility complex (MHC). Recent biochemical studies demonstrated that I-J is a homodimer of MW 84,000-90,000 composed of 42,000-46,000 MW glycopeptide subunits. The molecule is different from class II-restricted T-cell receptor, class II antigens or putative mouse CD28. The ligation of I-J molecules with anti-I-J results in the suppression of T-cell responses by the inhibition of early signal transduction through antigen recognition.

Animals↗

Human herpesvirus-6 infection (exanthem subitum) without rash.

Two patients with a three-day febrile episode in whom exanthem subitum was expected showed no appearance of skin eruption after subsidence of the fever. Virus was isolated from peripheral blood mononuclear cells in the acute stage, which was identified by the cytopathic effects of infected cells and the specific immunofluorescent staining of the cells with convalescent sera from exanthem subitum, but the virus could not be isolated from those in the convalescent stage. The morphology of the virus was similar to herpes group virus. There were seroconversions against representative strain of the causative agent of exanthem subitum in the two patients. The results indicated the presence of atypical clinical course of exanthem subitum.

Antibodies, Viral↗

Distribution of antibodies to a causative agent of exanthem subitum (human herpesvirus-6) in healthy individuals.

The transfer of IgG antibodies to a causative agent of exanthem subitum (human herpesvirus-6) from mother to infant was examined with an indirect immunofluorescence assay. Of 20 mothers, 85% had the antibody more than 1:10, and the significantly higher level of the antibody was found in the cord blood with a positive rate of 95%. A mean ratio of cord blood to maternal antibody titer was 1.63. A total of 301 sera from healthy individuals was examined for the age-specific prevalence of antibody to the virus. In the first 2 months of life, 87% of infants had the antibody; the positive rate and the level of antibody decreased during the first 6 months of life with the lowest positive rate of 6% at 4 to 5 months of age. After 6 months of age, they increased gradually and reached the highest level at 1 year of age with the positive rate of 86%. From 2 years of age, the prevalence of the antibody was almost stable (69% to 76%) and similar to those in adolescents and adults.

Adolescent↗

Fatal graft-versus-host disease following transfusion during open heart surgery.

We report fatal transfusion-associated graft-versus-host disease (GVHD) in a patient who was not severely immunosuppressed. A 58-year-old man received 800 ml of fresh whole blood from his son and an unrelated volunteer donor during open heart surgery. On the 10th day after the operation, he suddenly had a high fever, followed by generalized skin rash and liver dysfunction. Pancytopenia due to bone marrow aplasia developed a week later. A skin biopsy revealed a cutaneous lesion highly compatible with acute GVHD. The patient did not respond to high-dose methylprednisolone therapy, and died of multiple organ failure on the 18th day after the operation.

Graft vs Host Disease↗

[Clinical evaluation of cefixime in the treatment of acute uncomplicated cystitis].

Cefixime (CFIX) was administered 200 mg (2 divided doses) per day to 154 female patients with acute uncomplicated cystitis. Ninety four of the 154 patients who satisfied the criteria proposed by the UTI Committee, Japan were examined for the efficacy of the treatment, but 151 of 154 patients were included in the study of the side effects of the drug. The overall clinical efficacy was excellent in 80.8% and moderate in 18.1% of the patients. Ninety five (97.9%) of 97 strains which were isolated from the patients were eradicated in the urinary specimens by the treatment. Subjective side effects were observed in only one (0.7%) of the 151 patients, who complained of a sensation of heaviness in the head. No drug-related aggravation in the laboratory test was observed except for three patients who showed mild elevation glutamic pyruvic transaminase, alkaline phosphatase and blood urea nitrogen. These results showed that the oral administration of CFIX was excellent and satisfactory in the treatment for acute uncomplicated cystitis.

Acute Disease↗

Expression of cytokine genes in hematological malignancies.

A substantial number of leukemic blast colonies were formed when conditioned medium of human bladder carcinoma cell line 5637 was added as a stimulator. Recombinant colony-stimulating factor (CSF) also stimulated leukemic blast cell proliferation, leading to colony formation. Furthermore, serum CSF levels in some patients with acute myelogenous leukemia (AML), as detected by sensitive enzyme-linked immunosorbent assay (ELISA), were high. These observations prompted us to study further the expressions of hematopoietic growth factor genes. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in the leukemic blast cells from about 30% of patients with AML by Northern blot analysis using strict hybridization conditions with or without in vitro blast cell enrichment. These findings suggest that the expression of cytokine genes including the GM-CSF gene reflects in vivo phenomena, although no clear relationship between expression of the genes and serum CSF level has been established. Gene encoding tumor necrosis factor alpha (TNF-alpha), lymphotoxin (LT) and transforming growth factor beta (TGF-beta) were sometimes expressed in some malignant hematological cell lines and also some fresh leukemic cells.

Biological Factors↗

Dosage regimen of ranitidine in patients with renal impairment.

The validity of the Giusti-Hayton method for dosage regimen adjustment in patients with renal impairment was investigated using ranitidine. Five normal healthy volunteers received a single ranitidine recommended dose of 150 mg, and 20 patients with renal disease received single administration in doses individually calculated by the Giusti-Hayton method from each patient's creatinine clearance level, and the various pharmacokinetic parameters were compared. As a result, the area under the time-concentration curve 0----infinity (AUC0----infinity) in the renal disease patients was almost comparable to that in the normal healthy volunteers. The Giusti-Hayton method was considered useful to keep both the AUC0----infinity constant and the mean blood level of the drug in a steady state, in any degree of renal impairment.

Administration, Oral↗