Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 991 records · Page 55Linked to original sources

PubMed1991

Mutagenicity of (p-nitrophenyl)adenines in Salmonella typhimurium.

Adenine derivatives having a p-nitrophenyl group at position 2, 8, or 9 were directly mutagenic towards Salmonella typhimurium strains TA98 and TA100, whereas N6-(p-nitrophenyl)adenine was not mutagenic. 2,9- And 8,9-bis-(p-nitrophenyl)adenines were also mutagenic, but N6,9-bis-(p-nitrophenyl)adenine was not. The study on 13 (p-nitrophenyl)adenine derivatives for their Salmonella mutagenicity indicates that only those having a p-nitrophenyl ring directly linked to the purine ring are mutagenic, implying the importance of the coplanar character of the nitrophenyl and the purine rings. The nitro group seems essential for the mutagenicity, as shown from the results of assays using nitroarene-sensitive and -insensitive Salmonella strains. The mutagenic potency of this class of compounds is high, comparable to that of 2-nitrofluorene.

Adenine↗

PubMed1991

Nucleosides and nucleotides. 94. Radical deoxygenation of tert-alcohols in 1-(2-C-alkylpentofuranosyl) pyrimidines: synthesis of (2'S)-2'-deoxy-2'-C-methylcytidine, an antileukemic nucleoside.

(2'S and 2'R)-2'-Deoxy-2'-C-methylcytidine (1i and 15) and (2'S)-2'-deoxy-2'-C-ethylcytidine (1j) have been synthesized from the corresponding 2'-C-alkylarabinofuranosyl- or -ribofuranosylpyrimidine derivatives 3 and 4 by radical deoxygenation of the methyl oxalyl esters of the 2'-tert-alcohol, followed by sequential deblocking and amination at the 4-position. (2'S)-2'-Deoxy-2'-C-methyl-5-methyluridine (8) has also been synthesized in a similar manner. Among them, compound 1i exhibits the most potent cytotoxicity to L1210 cells with potency comparable to that of 1-beta-D-arabinofuranosylcytosine (1a). The size of the 2'-substituents and the configuration at the 2'-position are the most important for the cytotoxicity. Cytotoxicity in vitro of 1i against various human cancer cell lines was also examined and compared with that of 1a and 5-fluorouracil.

Animals↗

PubMed1991

Nucleosides and nucleotides. 96. Synthesis and antitumor activity of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and its derivatives.

The palladium-catalyzed cross-coupling reaction of 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4- carboxamide (8) with various terminal alkynes in the presence of bis(benzonitrile)palladium dichloride in acetonitrile containing triethylamine gave the desired 5-alkynyl derivatives 9 in high yields. However, when (trimethylsilyl)acetylene was used, the only isolable product was the undesired dimer, 1,2-bis(4-carbamoyl-1-beta-D-ribofuranosylimidazol-5-yl)acetylene derivative 10a. To circumvent such dimer formation, the reaction was done with use of trimethyl-[(tributylstannyl)ethynyl]silane in the absence of triethylamine to afford the desired 5-(2-trimethylsilyl)ethynyl derivative 9a in good yield. Furthermore, the similar cross-coupling reaction of 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboni tri le (12) with (trimethylsilyl)acetylene also afforded the desired nucleoside 13a. Deprotection of these compounds furnished 5-alkynyl-1-beta-D-ribofuranosylimidazole-4-carboxamides (6b-k) and -carbonitriles (14b-f). Among these, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (6b, EICAR) is the most potent inhibitor of growth of the various tumor cells in culture including human solid tumor cells. Preliminary results of in vivo antitumor activity against murine leukemias L1210 and P388 are also described.

Animals↗

PubMed1991

Nucleosides and nucleotides. 97. Synthesis of new broad spectrum antineoplastic nucleosides, 2'-deoxy-2'-methylidenecytidine (DMDC) and its derivatives.

A new type of antineoplastic nucleoside, 2'-deoxy-2'-methylidenecytidine (DMDC) has been synthesized from the corresponding 2'-keto pyrimidine nucleosides 3 and 8 by the Wittig reaction. During the course of the reaction, we found that an intermediate betaine could pick a proton from the excess triphenylphosphonium bromide to form the 2'-phosphonium salts 5 and 10, which could be further converted into the 2'-deoxy-2'-methylidene nucleosides 4 and 9 by treatment with sodium hydride. Various 5-substituted DMDC derivatives 19a-e,h and their uracil congeners 16a-h were also synthesized from the corresponding 5-substituted uridines 12a-f,h. Among them, DMDC as well as 2'-deoxy-2'-methylidene-5-fluorocytidine (19a) showed potent antileukemic activity against murine L1210 cells in culture. The activity of DMDC and 19a toward various human tumor cells in culture compared with 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil was also examined. In vivo antitumor activity of DMDC against L1210 was also described.

Animals↗

PubMed1991

Nucleosides and nucleotides. 95. Improved synthesis of 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)cytosine (cytarazid) and -thymine. Inhibitory spectrum of cytarazid on the growth of various human tumor cells in vitro.

Reaction of N3-benzoyl-1-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-beta- D- ribofuranosyl]thymine (4a) with diphenyl phosphorazidate, diethyl azodicarboxylate, and triphenylphosphine in tetrahydrofuran afforded N3-benzoyl-1-[2-azido-2-deoxy-3,5-O- (tetraisopropyldisiloxan-1,3-diyl)-beta-D-arabinofuranosyl]t hymine (5a) in good yield. After the sequence of deblocking of 5a gave 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)thymine (7), it was heated in N,N-dimethylformamide to produce 6,2'-imino-1-(2-deoxy-beta-D-arabinofuranosyl)thymine (8). This reaction disclosed the arabino configuration for 5a. Similarly the N3-benzoyluracil derivative 4b was transformed to the corresponding 2'-"up"-azidouridine derivative 5b, which was further converted to 1-(2-azido-2-deoxy-1-beta-D-arabinofuranosyl)cytosine (1, cytarazid). The antineoplastic activity of 1 was compared with that of ara-C against various human cancer cell lines in vitro.

Adenocarcinoma↗

PubMed1991

Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery.

Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent.

Aged↗

PubMed1991

1H-NMR study of the intramolecular interaction of a substrate analogue covalently attached to aspartic acid-101 in lysozyme.

We prepared the lysozyme derivative in which the beta-carboxyl group of Asp101 was modified with alpha-O-methyl N-glycylglucosaminide as an amide by means of the carbodimide reaction (alpha-MGG lysozyme). Since Asp101 residue is located at the edge of the active site cleft, a 1H-NMR study was carried out for this derivative in order to investigate the interaction between the introduced substituent and the active site cleft. It was confirmed that the alpha-MGG moiety sat in the active site cleft in alpha-MGG lysozyme from the reduction of line broadening of the NH-proton of Trp63 located in the active site cleft, the remarkable chemical shift change of the methyl group of the alpha-MGG moiety upon adding a trimer of N-acetyl-D-glucosamine [(NAG)3], and the NOE between the C6-proton resonance of Trp63 and the methyl resonance of the alpha-MGG moiety. Furthermore, alpha-MGG lysozyme had increased thermal stability compared with native lysozyme. Therefore, it was concluded that the alpha-MGG moiety covalently attached to Asp101 interacted with the active site cleft to increase the thermal stability of lysozyme.

Animals↗

PubMed1991

Preparation and properties of a lysozyme derivative in which two domains are cross-linked intramolecularly between Trp62 and Asp101.

A lysozyme derivative in which two domains were cross-linked intramolecularly was newly prepared by means of a two-step reaction. First, the beta-carboxyl group of Asp101 in lysozyme was selectively modified with 2-(2-pyridyldithio)ethylamine in the presence of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride. After reduction of the pyridyldithio moiety of Asp101 modified lysozyme at pH 4.5 with dithiothreitol, the derivative was allowed to cross-link intramolecularly by reaction with 1,3-dichloroacetone at pH 7. Intramolecularly cross-linked lysozyme thus formed was purified by gel chromatography followed by ion-exchange chromatography. Based on the results of 1H-NMR and peptide analyses, it was concluded that Asp101 was cross-linked to Trp62 with a -CH2COCH2SCH2CH2NH-bridge in this derivative. The derivative showed minor but distinct activity against Micrococcus lysodeikticus and glycol chitin. Its melting temperature for thermal denaturation was higher by 7.3 degrees than that of native lysozyme at pH 3.

Amino Acid Sequence↗

PubMed1991

Histological factors contributing to favorable prognoses of soft tissue sarcomas in premenopausal patients.

The correlations of sex with various histologic factors in soft tissue sarcomas (STS) were studied in 142 adult patients over the age of 20 years. They included 63 with malignant fibrous histiocytomas, 20 with liposarcomas, 20 with synovial sarcomas, 11 with malignant Schwannomas and 28 with other forms of STS. These were divided into four groups, according to age (20-49 years and greater than or equal to 50 years) and sex. Survival rates in female patients were better than those in male patients, and the difference was significant between the 20-49 year groups (p less than 0.01). The relative frequencies in distribution of each histologic type were similar among male and female patients in both age groups. Among histological factors, mitotic counts showed a significant correlation (P less than 0.04) with sex, followed by cellularity. STS in female patients aged 20-49 years had lower mitotic counts than in patients in other groups, where it occurred with a higher frequency of low and intermediate grade tumors. The findings suggested estrogen, either directly to indirectly, to have a favorable effect on STS prognosis in premenopausal female patients.

Adult↗

PubMed1991

Plasma endothelin levels in healthy children: high values in early infancy.

We measured plasma endothelin-1-like immunoreactivity (ET-1-LI) levels in the peripheral vein of 70 healthy children (37 males and 33 females) aged 5 days to 15 years to establish the normal range in children, and compared them with those in 11 normal adults (age, mean +/- SD; 29.5 +/- 5.7 years, 6 males and 5 females). Plasma ET-1-LI levels (pg/ml, mean +/- SD) in children of each age group and adults were as follows: children younger than 1 month = 23.4 +/- 3.9 (n = 10), 1-3 months = 25.0 +/- 6.1 (n = 8), 3-6 months = 17.0 +/- 1.4 (n = 8), 6 months to 1 year = 14.0 +/- 1.7 (n = 13), 1-5 years = 13.8 +/- 2.6 (n = 11), 5-10 years = 13.6 +/- 1.6 (n = 10), 10-15 years = 12.9 +/- 2.2 (n = 10), and adults = 13.2 +/- 2.4 (n = 11). There was no significant difference in plasma ET-1-LI levels between males and females in each age group. Plasma ET-1-LI levels in children younger than 3 months were significantly (p less than 0.01) higher than those in older children or adults. After 3 months of age, plasma ET-1-LI levels were nearly constant at all ages. This is the first report to establish the normal range of plasma ET-1-LI levels in children.

Adolescent↗

PubMed1991

Efficacy of bypass between extracerebral artery and cerebral vein with retrograde verapamil infusion into focal cerebral ischemic tissue in rats.

We examined the efficacy of a bypass from an extracerebral artery to a cerebral vein (EA-CV) with retrograde verapamil infusion on acute focal cerebral ischemia in 35 rats. In 12 rats, within 1 hour after occlusion of the middle cerebral artery (MCAO), changes in blood-brain barrier permeability were examined by [14C]alpha-aminoisobutyric acid autoradiography after EA-CV bypass surgery; there were no significant changes during a period of 2 hours after EA-CV bypass. The other 18 rats having MCAO were divided into three groups of six each. Group A rats (control) underwent only cannulation of the cerebral vein. Group B rats had an EA-CV bypass. Group C rats received verapamil (0.1 mg/kg every 2 h) by transvenous perfusion of the brain (TVPOB) through the EA-CV bypass. In all rats in Groups A and C, local cerebral blood flow (LCBF) and quantitative measurement of early cerebral infarct volume were performed by autoradiography using [14C]iodoantipyrine and histochemical staining methods. Group B rats were examined only with the LCBF measurement. Group B (EA-CV bypass only) showed a nonsignificant improvement (18-40%) of LCBF in the ischemic cerebral cortical areas as compared with control Group A. Group C (EA-CV bypass with TVPOB with verapamil) showed an extensive and significant improvement in LCBF in the ischemic cortical areas (115-140%; P less than 0.05) and a slight increase in LCBF in the subcortical areas (17-29%), with a significant reduction (greater than 35%; P less than 0.05) in a total cerebral infarct volume in the ischemic cerebral hemisphere as compared with the control Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Measurement of hepatic blood flow by use of per-rectal portal scintigraphy with 133Xe.

A relatively noninvasive method is needed to evaluate the hepatic blood flow of patients with liver disease. We used per-rectal portal scintigraphy with 133Xe, and analysed the time-activity curves of the liver and portal vein. To do this, wash-out curves of the liver were plotted, and the hepatic blood flow and the ratio of the blood flow to the right lobe of the liver to that to the left lobe (R/L ratio) were calculated. The mean hepatic blood flow was 137 +/- 23 ml/100 g/min for four patients with fatty liver, 139 +/- 16 ml/100 g/min for seven patients with chronic persistent hepatitis, 120 +/- 15 ml/100 g/min for ten patients with chronic aggressive hepatitis, and 75 +/- 21 ml/100 g/min for 14 patients with cirrhosis. All seven patients with hepatic blood flow that was less than 100 ml/100 g/min and an R/L ratio less than 1.0 had cirrhosis. Only two of the 22 patients with hepatic blood flow that was greater than 100 ml/100 g/min and an R/L ratio greater than 1.0 had cirrhosis. Per-rectal portal scintigraphy can be used to measure the hepatic blood flow, but it was not useful for the diagnosis of fatty liver.

Administration, Rectal↗

PubMed1991

Beta-adrenergic stimulation induces intracellular Ca++ increase in human epidermal keratinocytes.

Intracellular Ca++ ([Ca++]i) is one of the most important second messengers of extracellular signals that induce cellular responses. In epidermal keratinocytes, both extracellular and intracellular Ca++ are reported to be important to cell differentiation and proliferation. Several mechanisms that increase [Ca++]i have been elicited in various tissues; however, in epidermal keratinocytes they remain unknown. Thus, we investigated the [Ca++]i modulation in cultured human epidermal keratinocytes and the stimulation that increases the concentration. The [Ca++]i concentration of keratinocytes was increased immediately and transiently by epinephrine. Methoxamine hydrochloride and clonidine (alpha-1- and 2-adrenergic agonists) did not induce an increase in [Ca++]i. The beta-antagonist, propranolol, inhibited the [Ca++]i increase induced by epinephrine and salbutamol (a beta-2-agonist). These results reveal that the beta-adrenergic stimulation induces an immediate and transient [Ca++]i increase in human keratinocytes. Beta-adrenergic stimulation is known to induce adenylate cyclase activation, which results in cyclic AMP accumulation through stimulatory guanosine 5-triphosphate (GTP) binding proteins in the keratinocytes. Also, epinephrine is reported to inhibit cultured epidermal cell proliferation. The effect of epinephrine has been demonstrated by cyclic AMP accumulation; however, beta-adrenergic stimulation revealed a [Ca++]i increase in keratinocytes in our study. One of epinephrine's regulatory effects on epidermal cell proliferation is assumed to occur through the [Ca++]i increase as well.

Adrenergic beta-Antagonists↗

PubMed1991

Comparison of clinical and pathological characteristics in incidentally detected and suspected renal carcinoma.

In a study of the clinical and pathological characteristics of incidentally detected and suspected renal carcinoma, we reviewed the manner of presentation, serum immunosuppressive acidic protein (IAP), tumour stage and size in 112 consecutive patients with renal carcinoma who were diagnosed clinically and surgically between 1980 and 1989. The results showed an increase in the proportion of incidentally diagnosed cases. The routine use of radiological imaging, especially ultrasound and computed tomography (CT), has led to tumours being diagnosed earlier than when IAP is used as a tumour marker in patients with incidentally detected renal carcinoma. Tumours were lower stage and smaller in patients with incidentally detected renal carcinoma than in patients in whom the diagnosis was suspected.

Adult↗

PubMed1991

Phosphoglycerates and protein phosphorylation: identification of a protein substrate as glucose-1,6-bisphosphate synthetase.

We have previously reported the occurrence of two endogenous protein phosphorylation systems in mammalian brain that are enhanced in the presence of 3-phosphoglycerate (3PG) and ATP. We present here a study of one of these systems, the phosphorylation of the 72-kDa protein (3PG-PP72). This system was separated into the substrate, 3PG-PP72, and a kinase by ammonium sulfate fractionation, hydroxyapatite chromatography, and hydrophobic interaction HPLC. The substrate protein was shown to be directly phosphorylated with [1-32P]1,3-bisphosphoglycerate [( 1-32P]1,3BPG) with an apparent Km of 1.1 nM. Nonradioactive 1,3BPG inhibited 32P incorporation in the presence of [gamma-32P]ATP and 3PG. Phosphopeptide mapping and phosphoamino acid analyses indicated that the site of phosphorylation of 3PG-PP72 observed in the presence of 3PG and ATP is a serine residue identical to that observed with [1-32P]1,3BPG. Moreover, [32P]phosphate incorporated into 3PG-PP72 in the presence of 3PG and ATP was removed by subsequent incubation with glucose-1-phosphate or glucose-6-phosphate. Finally, 3PG-PP72 showed chromatographic behaviors identical to those of glucose-1,6-bisphosphate (G1,6P2) synthetase. Based upon these observations, we conclude that 3PG-PP72 is G1,6P2 synthetase and that it is phosphorylated directly by 1,3BPG, which is formed from 3PG and ATP by 3PG kinase present in a crude 3PG-PP72 preparation.

Amino Acids↗

PubMed1991

[Hospital spread of scabies from an immunocompromised patient with Norwegian scabies].

Scabies was first found in a 71-year-old female who had been diagnosed as having leukemic transformation of primary myelofibrosis and had undergone treatment for the disease. She was admitted to the hospital in December 1986, because of abdominal fullness and a generalized subcutaneous tumor that proved to be myeloblastoma. For treatment of the underlying disease, the regimen of the combination of vindesine, cyclophosphamide, 6-mercaptopurine, and prednisolone was selected. She developed cardiac failure and fell into a coma one month after starting the anticancer therapy. She was put on artificial respiration and on additional steroid therapy as well. Dexamethasone was administrated at 16 mg/day. Since the myeloblastomas found on admission regressed, the steroid therapy was continued. She was in coma for a few days before her skin lesions turned red and formed a grayish crust in the lower abdominal region. Several days later, the doctor responsible for the treatment of this patient developed pruritus and exanthema on both arms, and soon many nurses in the same hospital-ward developed similar symptoms. At approximately the same time, the patient with myelofibrosis was diagnosed as having Norwegian scabies: the crusted skin lesions revealing many Sarcoptes scabiei mites. Two doctors (2/18), 17 nurses (17/19) and 3 other patients (3/51) were found to have contracted scabies, and we recognized the hospital spread of the infection. The first patient was isolated in a private room, and we avoided direct contact with her. The persons with scabies were treated with crotamiton liniment. The first scabies patient died of cardiac failure 1 month after falling into a coma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds.

A series of novel compounds, 5-alkynyl-1-beta-D-ribofuranosylimidazole-4- carboxamides, have been identified as broad-spectrum antiviral agents. 5-Ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide (EICAR), the most potent congener of the group, showed antiviral potency about 10- to 100-fold greater than that of ribavirin. Similar in spectrum to ribavirin, EICAR was particularly active (50% inhibitory concentration, 0.2 to 4 micrograms/ml) against poxviruses (vaccinia virus), togaviruses (Sindbis and Semliki forest viruses), arenaviruses (Junin and Tacaribe viruses), reoviruses (reovirus type 1), orthomyxoviruses (influenza A and B viruses), and paramyxoviruses (parainfluenza virus type 3, measles virus, subacute sclerosing panencephalitis virus, and respiratory syncytial virus). EICAR was also cytostatic for rapidly growing cells (50% inhibitory concentration, 0.2 to 0.9 microgram/ml). EICAR inhibited vaccinia virus tail lesion formation at doses that were not toxic to the host. EICAR is a candidate antiviral drug for the treatment of pox-, toga-, arena-, reo-, orthomyxo, and paramyxovirus infections.

Adenosylhomocysteinase↗

PubMed1991

Incomplete testicular feminization syndrome. A case occurring in a family with frequent hypospadias.

The case of a 16-year-old patient with incomplete testicular feminization syndrome is reported. The patient had phenotypically female genitalia except for clitoromegaly. Hormonal examinations revealed low plasma testosterone levels but a normal concentration of 5 alpha-dihydrotestosterone, and radiological and surgical examinations revealed no development of Müllerian structures including the uterus and the adnexa. This happened in a family with a frequent occurrence of both hypospadias and cryptorchism.

Adolescent↗