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Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 721 records · Page 40Linked to original sources
PubMed1994

Clinical pharmacology of 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, an orally administered long-acting derivative of low-dose 1-beta-D-arabinofuranosylcytosine.

1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (cytarabine ocfosfate, stearyl-ara-CMP) is a newly synthesized 5'-alkylphosphate derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), which is lipophilic, resistant to inactivation by deamination, and orally active. Pharmacology of this drug was studied in patients with hematological malignancies. The concentrations of stearyl-ara-CMP, ara-C (its active metabolite), and 1-beta-D-arabinofuranosyluracil (ara-U, its inactive metabolite) were determined by radioimmunoassay. When six patients received a single p.o. dose of the drug (500 mg/m2), stearyl-ara-CMP, ara-C, and ara-U could be detected in the plasma for at least 72 h afterwards. The plasma disappearance curve of stearyl-ara-CMP corresponded to a one-compartment open model with first-order absorption kinetics. The peak plasma level (Cmax) was 322 +/- 218 nM, and the predicted time to reach Cmax (Tmax) was 6.5 +/- 4.5 h, while the elimination half-life (t1/2) was very long (32.0 +/- 8.4 h). The plasma ara-C level increased slowly to a Cmax of 26.3 +/- 12.7 nM (Tmax, 13.3 +/- 4.7 h) after stearyl-ara-CMP administration. This level was quite low compared with that achieved by low-dose s.c. ara-C therapy, but ara-C persisted longer in the plasma in the former case, and the area under the curve was similar for both regimens. For ara-U, the Cmax, Tmax, and t1/2 were 483 +/- 315 nM, 23.6 +/- 4.0 h, and 19.6 +/- 5.3 h, respectively. No stearyl-ara-CMP was detected in the urine, and only 8.0% of the administered dose was excreted as ara-C and ara-U within 72 h. The stearyl-ara-CMP concentration in the cerebrospinal fluid was below the limit of detection in three patients without meningeal involvement at 6 h. During clinical use of stearyl-ara-CMP, macrocytic anemia was observed, and some patients also developed megaloblastic change of their erythroblasts, suggesting a mild and persistent cytostatic effect. In conclusion, p.o. therapy with stearyl-ara-CMP achieved prolonged maintenance of the plasma drug level. Thus, the drug released a very low dose of ara-C over a long period in plasma and tissues and had a prolonged mild antineoplastic effect in patients with hematological malignancies.

Acute Disease↗
PubMed1994

Differential expression of interleukin-2 receptors (alpha and beta chain) in mature lymphoid neoplasms.

We investigated the expression of interleukin-2 receptors (IL-2R) in 60 adult patients with mature lymphoid neoplasms by flow cytometric analysis, using two monoclonal antibodies, anti-Tac for IL-2R alpha-chain (IL-2R alpha) and Mik-beta 1 for IL-2R beta-chain (IL-2R beta). Among B-cell malignancies, IL-2R alpha was found in 13/25 (52%) cases of chronic lymphocytic leukemia (CLL) and its variants, 3/14 (21%) of a heterogeneous group of non-Hodgkin's lymphoma (NHL) and none of the plasma cell diseases. IL-2R beta was not observed in any of B-cell neoplasms. IL-2R alpha was more frequently expressed in CD11b(+) B-cell neoplasms than in CD11b(-) (P < 0.05). In T-cell disorders, all three cases of adult T-cell leukemia/lymphoma expressed IL-2R alpha but not IL-2R beta. IL-2R beta was detected in 3/8 cases of CLL and 2/3 of NHL and none of these cases expressed IL-2R alpha. CD8(+) malignant T-cells commonly displayed IL-2R beta. These data indicate that the IL-2R alpha and IL-2R beta in mature lymphoid neoplasms was expressed independently each other and was associated with the particular phenotypical characteristics of neoplastic cells, respectively.

Adult↗
PubMed1994

Age-related acute adriamycin cardiotoxicity in mice.

Myocardial mitochondrial function after acute adriamycin exposure was compared in infant and adult mice. Heart mitochondrial were isolated 48 h after an intraperitoneal injection of adriamycin. Concentrations of adriamycin in serum and heart tissue were not significantly different between infant and adult mice. Oxygen consumption (state 3 respiration), and respiratory control ratio (RCR) were studied polarographically. Enzyme activities in the respiratory chain [succinate-cytochrome c reductase (SCCR), NADH-cytochrome c reductase (NCCR), cytochrome c oxidase (CCO)], and adenine nucleotide translocase (ANT) were assayed. After saline injection (control), no significant differences were detected in state 3 respiration, RCR, and enzyme activity of ANT between infant and adult mice. The respective enzyme activities of SCCR, NCCR, and CCO in adult mice were significantly lower than those in infant mice. After adriamycin injection in adult mice, there were significant decreases in state 3 respiration (using glutamate and malate as substrates from 239 +/- 25 to 160 +/- 50 nanoatom O2/min/mg protein), RCR (using glutamate and malate as substrates from 7.2 +/- 1.0 to 4.4 +/- 1.4), and enzyme activities of SCCR (from 279 +/- 30 to 178 +/- 28 nmol/min/mg protein) and NCCR (from 331 +/- 43 to 237 +/- 30 nmol/min/mg protein), but there were no significant changes in infant mice. No significant changes in enzyme activities of CCO and ANT were found in either infant or adult mice following the administration of adriamycin. In conclusion, adriamycin is less toxic on the myocardial mitochondrial function in infant mice than in adult mice.

Acute Disease↗
PubMed1994

Histochemical analysis of glycoproteins in the unicellar glands in the epidermis of an Indian freshwater fish Mastacembelus pancalus (Hamilton).

The unicellular glands in the epidermis of the Indian freshwater fish Mastacembelus pancalus consist of three types of mucous cells and sacciform cells. The histochemical properties of their secretory glycoproteins have been analysed by means of a battery of histochemical methods. These included methods for the identification and simultaneous visualization of oxidizable vicinal diols, O-acyl sugars, O-sulphate esters and sialic acid residues with or without side-chain O-acyl variants. Four general classes of glycoproteins (GPs) were identified. These included (i) GPs with O-sulphate esters and oxidizable vicinal diols, (ii) GPs with oxidizable vicinal diols and sialic acid residues with or without O-acyl substitution at C7, (iii) GPs mainly with O-sulphate esters, low moieties of GPs with oxidizable vicinal diols, O-acyl sugars and sialic acid residues with side-chain O-acyl variant predominantly at C8 (or which are di- or tri-substituted) or C9 and in traces of sialic acid residues without O-acyl substitution or with O-acyl substitution at C7, and (iv) GPs with traces of oxidizable vicinal diols, O-acyl sugars and sialic acid residues with O-acyl substitution at C8 (or which are di- or tri-substituted) or C9. The physiological significances of these GP classes and their release on the surface of the epidermis are discussed with special reference to their role in lubrication, protection and inhibition of the invasion and proliferation of pathogenic microorganisms in the epidermis, as adapted to the peculiar mode of life of the fish.

Animals↗
PubMed1994

Relationship among coelacanths, lungfishes, and tetrapods: a phylogenetic analysis based on mitochondrial cytochrome oxidase I gene sequences.

To clarify the relationship among coelacanths, lungfishes, and tetrapods, the amino acid sequences deduced from the nucleotide sequences of mitochondrial cytochrome oxidase subunit I (COI) genes were compared. The phylogenetic tree of these animals, including the coelacanth Latimeria chalumnae and the lungfish Lepidosiren paradoxa, was inferred by several methods. These analyses consistently indicate a coelacanth/lungfish clade, to which little attention has been paid by previous authors with the exception of some morphologists. Overall evidence of other mitochondrial genes reported previously and the results of this study equally support the coelacanth/lungfish and lungfish/tetrapod clades, ruling out the coelacanth/tetrapod clade.

Amino Acid Sequence↗
PubMed1994

Prophylactic intravesical chemotherapy with adriamycin plus verapamil for primary superficial bladder cancer: preliminary results. The Kyushu University Urological Oncology Group.

A prospective randomized trial was conducted to compare the prophylactic effect of intravesical installation of Adriamycin (ADM) plus verapamil (VR) with that of ADM alone for recurrence of superficial bladder cancer. A total of 226 patients were enrolled and randomized into 2 groups. Group A received intravesical instillation of ADM (30 mg/30 ml physiological saline) on 19 occasions during a 1-year period after transurethral resection, whereas group B received intravesical instillation of ADM (30 mg/24 ml physiological saline) plus VR (15 mg/6 ml saline) according to the same schedule used for group A. Evaluation was possible in 157 of the 226 registered patients (group A, 76; group B, 81). There was no significant difference in the patients' characteristics between the two groups, and there was no significant difference in the overall nonrecurrence rate determined over a 24-month follow-up period. However, group B showed a significantly higher nonrecurrence rate than did group A for tumors measuring less than 1 cm in diameter (P < 0.05) and for histological grade 2 tumors (P < 0.01) in spite of there being no significant difference in the other characteristics of each subgroup of patients. The incidence and severity of side effects were similar in both groups, and VR caused no significant systemic toxicity. Although further follow-up is necessary, these results suggest that intravesical instillation of ADM plus VR is clinically safe and may be more effective than instillation of ADM alone in preventing the postoperative recurrence of superficial bladder cancer (less than 1 cm in diameter, histological grade 2).

Administration, Intravesical↗
PubMed1994

The clinicopathologic features of serum CA 19-9-positive colorectal cancers.

The preoperative serum levels of carbohydrate antigen 19-9 (CA 19-9) were determined in 206 patients with colorectal cancer, 52 (25.2%) of whom were found to be positive. All of these patients had advanced cancers and significantly higher incidences of tumor invasion through the muscularis propria (91.3%) and lymph node involvement (54.5%). The incidences of liver metastasis and Dukes' stage D in the CA 19-9-positive group were 38.5% and 42.9%, respectively, significantly higher than those in the CA 19-9-negative group of 6.5% and 14.8%, respectively. Moreover, the incidence of liver metastasis in the CA 19-9-positive group patients with Dukes' stage D cancer was 95.2% (20/21); CA 19-9 showing higher specificity (81.7%) and a more positive predictive value (38.5%) for liver metastasis than the carcinoembryonic antigen (CEA). When a cutoff value of 160 U/ml was used, the specificity and positive predictive value reached 97.7% and 81.0%, respectively. An analysis of response operating characteristic (ROC) curves for liver metastasis revealed that CA 19-9 was more useful than CEA. The long-term survival of the CA 19-9-positive group patients was significantly worse than that of the CA 19-9-negative group patients (P < 0.0001), with no 1.25-year survivors in the former group when the cutoff value of 160 U/ml was used. These results suggest that serum CA 19-9 as a useful preoperative indicator of liver metastasis and prognosis in colorectal cancer.

CA-19-9 Antigen↗
PubMed1994

Use of immobilized histidine in assay for endotoxin in patients with liver disease.

The Limulus amebocyte lysate (LAL) test has the disadvantage of being influenced by various inhibitors and activators. We have developed a method for the LAL reaction that involves the specific adsorption and isolation of endotoxin using a membrane filter unit and immobilized histidine; in this present study we used the method to measure endotoxin in the plasma of patients with acute or chronic liver disease. The adsorbed endotoxins are separated from LAL-inhibitors or -activators by the membrane filter unit, and their activity is directly assayed with the LAL reagent in a filter cup without any inhibition or activation. The study population consisted of 23 subjects, 3 with fulminant hepatitis and 20 with cirrhosis (9 with esophageal varices and 11 without). All 3 (100%) of the samples of plasma from patients with fulminant hepatitis were positive for endotoxin, as were the samples of 7 (78%) of the 9 patients with cirrhosis and esophageal varices, and 2 (18%) of the 11 patients with cirrhosis but without such varices. The results suggested that this method appears to be useful for assaying the concentration of endotoxin in patients with fulminant hepatitis or cirrhosis of the liver.

Acute Disease↗
PubMed1994

Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis.

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1 beta was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-alpha was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.

Adenocarcinoma↗
PubMed1994

Clinical significance of urinary enzymes and beta 2-microglobulin following ESWL.

To examine the renal damage caused by shock waves, urinary excretion of enzymes and beta 2-microglobulin were determined before and after ESWL. Urine samples were obtained from 35 patients with renal stone and 26 patients with ureteric stone treated with ESWL. Urinary lactate dehydrogenase (LDH) levels significantly increased on day 0, just after ESWL, in both groups. In the ureteric stone group the kidneys received less shock waves than in the renal stone group. Increased urinary lactate dehydrogenase was considered to have derived from erythrocytes in urine. Elevated urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were also observed on day 0 after ESWL in both groups, due to unknown reasons. Indirect effect of ESWL through the sympathetic nervous system or humoral factors may contribute to increases in the urinary excretion of NAG. No significant increase was found in urinary gamma-glutamyl-transpeptidase (GGTP) levels for 5 days after ESWL. Urinary beta 2-microglobulin (BMG) levels increased on day 0 in the renal stone group alone. In our present study, the clinical significance of urinary enzymes and BMG was not well evaluated, because urinary excretion of these indicators following ESWL were transient and mild.

Acetylglucosaminidase↗
PubMed1994

Clinical study of asymptomatic microscopic haematuria.

A clinical statistical survey was performed on 355 patients with asymptomatic microscopic haematuria. Urologic lesions were detected in 19.4% of the patients. Urologic lesions requiring surgical treatment were found in only two patients with bladder carcinoma and with renal calculus. With the exception of glomerulonephritis, the proportion of those over 40 years who had urologic lesions was higher. It is suggested that an initial evaluation based on excretory urography, cystoscopy and ultrasonography is more important for patients over 40 years.

Adolescent↗
PubMed1994

Releases of oxytocin and prolactin during breast massage and suckling in puerperal women.

The responses of prolactin (PRL) and oxytocin (OT) to suckling and breast massage were examined in lactating women. The suckling group showed increase in frequency of pulsatile release of OT and increase of the plasma PRL level. In contrast, the breast massage group showed a significant, but not a pulsatile increase in the plasma OT level and no increase in the plasma PRL level. These findings suggest that suckling causes both milk production and milk ejection, while breast massage causes only ejection of milk already stored in acini, and that prolactin release is not related to increase of the oxytocin level itself, but to its pulsatile release.

Breast↗
PubMed1994

Influence of idarubicinol on the antileukemic effect of idarubicin.

We investigated the antileukemic potency of idarubicinol (IDAol), a 13-dihydro (13-OH) metabolite of idarubicin (IDA), on the HL60 line of human leukemia cells. In contrast to daunorubicinol (DNRol) and to doxorubicinol (DOXol), IDAol showed an extensive accumulation in HL60 cells. The high affinity for DNA and the strong DNA cleavage activity of IDAol were comparable to values for IDA; consequently, IDAol was strongly cytotoxic against HL60 cells. IDAol may play an important role in the clinical efficacy of IDA in patients with acute leukemia, particularly since it persists in the blood for prolonged periods after the administration of IDA.

DNA↗
PubMed1994

Unique structure of new serine tRNAs responsible for decoding leucine codon CUG in various Candida species and their putative ancestral tRNA genes.

In an asporogenic yeast, Candida cylindracea, codon CUG is not translated as leucine but as serine. On the basis of our recent work on the determination of the genetic code using in vitro translation systems coupled with isolation of the corresponding tRNA molecules, it appears that this non-universal genetic code is unitized not only in C cylindracea but also in various Hemiascomycetes. Here we show that in addition to the species already reported, three pathogenic yeasts, C guilliermondii, C lusitaniae and C tropicalis, have tRNA(Ser)CAG, indicating that this non-universal genetic code (CUG=Ser) also exists in these species. Determination of their primary structures revealed that the uridine conserved at position 33 in usual tRNAs, is replaced by guanosine or cytidine. This suggests that the three-dimensional structures of the anticodon loop of these tRNAs differ from the conventional structure comprising the U turn in this position. Moreover, we succeeded in isolating putative ancestral serine tRNA genes whose sequences are highly homologous to tRNA(Ser)CAG in each case. These tRNA genes all have the anticodon sequence CGA corresponding to the codon UCG, indicating that tRNA(Ser)CAG might have emerged from tRNA(Ser)CGA during evolutionary change of the assignment of codon CUG.

Base Sequence↗
PubMed1994

Location of melittin fragment carrying spiropyran in phospholipid bilayer membrane determined by thermal isomerization.

Melittin fragments carrying spiropyran were synthesized, and their distribution in phospholipid bilayer membrane was studied by using spiropyran as a probe. Spiropyran was connected to the side chain of a Glu residue (Glu(OSp)), and the residue was replaced for the fourth position of melittin (1-7) fragment (M7Sp). M7Sp showed a high affinity for phospholipid membrane. The spiropyran group of M7Sp was converted to a merocyanin group by UV irradiation, which reduced the amount of the peptide bound to the membrane to the half of the initial amount. The location of the merocyanin group of M7Sp in the membrane was evaluated by the rate of thermal isomerization from merocyanin to spiropyran, which is sensitive to the microenvironment of merocyanin. A large fraction of the merocyanin group isomerized rapidly back to a spiropyran form, indicating that M7Sp is located in a relatively hydrophobic region of the membrane. Although the interaction of the peptide with phospholipid membrane is affected by photoisomerization of the spiropyran substituent, spiropyran was shown to be a useful tool to evaluate the location of the peptide in the lipid membrane.

Amino Acid Sequence↗