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Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 379 records · Page 21Linked to original sources
PubMed1986

Inhibition of Epstein-Barr virus infection in vitro by recombinant human interferons alpha and gamma.

The inhibitory effects of pure recombinant human interferons alpha A and gamma (reIFN-alpha A and -gamma) on Epstein-Barr virus (EBV) infection of a human EBV-negative B cell line, BJAB, and of normal adult B lymphocytes were studied. With pretreatment for 24 h, both types of reIFNs were effective in suppressing the production of EBV specific nuclear antigen (EBNA-1) in BJAB cells 24 h after EBV-infection, as determined by the immunoblotting technique. ReIFN-alpha A was, however, a much more potent inhibitor than reIFN-gamma. With treatment starting 1 h after EBV infection, both types of reIFNs were less effective in the suppression of EBNA production. Neither of the reIFNs showed any inhibitory effect on EBNA production in the latently EBV-infected cell lines, Raji and Daudi. These results suggest that reIFNs act in the early phase of EBV infection. Both types of reIFNs were also effective in inhibiting EBV infection of normal adult B lymphocytes as demonstrated by a reduction both in [3H]thymidine incorporation 6 days after EBV infection and in the total number of proliferating cells 21 days after EBV infection. Again, reIFN-alpha A showed a greater inhibitory effect than reIFN-gamma. We also showed that in BJAB cells, reIFN-alpha A strongly induced (2'-5')oligoadenylate synthetase activity, whereas reIFN-gamma increased the surface expression of HLA class I antigens.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

The effects of caerulein on nocturnal sleep.

Caerulein, a decapeptide chemically related to cholecystokinin octapeptide, was examined polysomnographically for its effect on nocturnal sleep in healthy volunteers. The subjects were 6 males (20-24 years of age). Either a placebo (saline) or caerulein 0.6 microgram/kg was administered intramuscularly to volunteers at 23:00. Polysomnograms were then recorded from 23:00 till 06:30. Little variation in sleep period time, total sleep time, sleep efficiency index, sleep latency, or REM sleep latency in the drug night were found as compared to the control night values. The percentage of REM stage sleep increased significantly (P less than 0.01) on the drug administered night, whereas the change in the percentages of each of the other stages was not significant. The REM density of the vertical eye movements tended to increase on the drug night, but the density of the horizontal eye movements showed no change. There were no changes in the spontaneous GSRs in either vola or dorsum manus. As caerulein shows alpha-1 adrenergic receptor blocker activity, it is suggested that caerulein may increase REM sleep by affecting the central noradrenergic neurons.

Adult↗
PubMed1986

Binding and crosslinking of 125I-labeled recombinant human tumor necrosis factor to cell surface receptors.

Highly purified recombinant human tumor necrosis factor (TNF) (molecular mass determined as 17 kilodaltons (kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and as 36 kDa by Sephadex G-100 gel chromatography) was labeled with 125I to a specific activity of 5 microCi/micrograms without appreciable loss of activity. The binding of 125I-TNF to eighteen human and twelve animal cell lines was examined. The binding varied considerably among different cell lines. In most cell lines, the binding was inhibited up to greater than 90% by the addition of a 100-fold excess of unlabeled TNF. Some human and mouse cell lines showed no significant binding above background levels, suggesting that these cell lines had no receptors for TNF. Among the TNF receptor-positive cell lines, there was no direct correlation between the level of specific TNF binding and the level of sensitivity to the cytotoxic or cytostatic effect of TNF. Some cell lines were sensitive to TNF, whereas others were not affected at all by TNF. The TNF receptor-negative cell lines were also resistant to TNF. Therefore, although the existence of TNF receptor seems to be necessary, it does not alone determine cellular sensitivity to TNF. Scatchard analysis of the binding data revealed that human HeLa S3 and THP-1 had about 50,000 and 10,000 receptors/cell with a dissociation constant (KD) of 0.3-0.5 nM, respectively. Similarly, mouse L-929 and L-M cells had about 5,000 receptors/cell with KD of 3-5 nM. 125I-TNF bound to HeLa S3 cells was rapidly internalized at 37 degrees C, presumably by receptor-mediated endocytosis, and degraded to acid-soluble products. The turnover of TNF receptors on HeLA S3 cells seemed to be rapid, since the level of specific binding quickly decreased after treatment with 100 micrograms/ml of cycloheximide at 37 degrees C with a half-life of about 1.5 h. The crosslinking of the cell-bound 125I-TNF with the use of disuccinimidyl suberate yielded a complex of 105 kDa for HeLa S3 and THP-1 cells, and a complex of 100 kDa for U937 cells. The crosslinking was completely inhibited by the addition of a 100-fold excess of unlabeled TNF. Assuming that the complex was due to a one-to-one association of the dimeric form of TNF (34 kDa) with the receptor, we estimated the molecular size of the human TNF receptor to be 71 kDa for HeLa S3 and THP-1, and 66 kDa for U937.

Animals↗
PubMed1986

Effects of valproate on biogenesis and function of liver mitochondria.

The mitochondrial protein content of liver increased, and mitochondria enlarged after prolonged administration of valproic acid (VPA: N-dipropylacetic acid) to rats. The mitochondria showed low specific activities of membrane-bound enzymes, decreased content of cytochrome aa3, and decreased respiration in states 3 and 4. In vitro studies of amino acid incorporation suggested a decrease in protein synthesis in liver mitochondria from VPA-treated rats. Prolonged administration of VPA seems to impair mitochondrial structure and function.

Amino Acids↗
PubMed1986

Serum neuron-specific enolase as a marker useful for monitoring the effectiveness of therapy in patients with neuroblastoma--as compared with urinary catecholamine metabolites.

Neuron-specific enolase (NSE) in sera of 3 patients with neuroblastoma (Stage IV) were measured by radioimmunoassay, as compared with urinary catecholamine metabolites (vanillyl-mandelic acid (VMA) and homovanillic acid (HVA] during the course of chemotherapy, radiation, and second look operation. In Case 1 (Stage IV B) and Case 3 (Stage IV A), NSE-level on admission was found to be elevated to 51.0 ng/ml and 25.5 ng/ml, respectively. VMA and HVA were also elevated. In Case 2 (Stage IV A), NSE on admission was elevated to 128.0 ng/ml., HVA was high, but VMA was within normal range. From 1 to 3 weeks after chemotherapy and radiation, high levels of urinary VMA and/or HVA in patients promptly decreased within normal range. The size of primary tumor masses either showed no marked change or slightly decreased by radiological examinations. After intensive chemotherapy, high levels of serum NSE decreased within normal range. At that time, second look operations were carried out. The size of primary tumors was reduced (3.6 X 2.7 X 2.1 cm in average) and almost all masses had scarred over. These data suggest that serum NSE levels correlate very well with residual tumor burdens.

Catecholamines↗
PubMed1986

Urine neuron-specific enolase and its clinical implication in patients with neuroblastoma.

Urine levels of neuron-specific enolase (NSE) were determined in 6 patients with neuroblastoma, in 72 controls and in 5 infants with hematuria by means of a double-antibody inhibition radioimmunoassay method. Urine levels (NSE ng/creatinine mg) in 2 patients with advanced neuroblastoma were elevated (3.03 +/- 0.28 (S.D.)), when compared with those of 4 patients with neuroblastoma in remission (0.65 +/- 0.26 (S.D.], 10 healthy neonates (1.26 +/- 0.42 (S.D.)), 25 healthy infants (0.51 +/- 0.26 (S.D.)), and 37 healthy adults (0.37 +/- 0.17 (S.D.)). Urine levels in 4 infants with microhematuria and an infant with macrohematuria were 1.62 +/- 0.10 (S.D.) and 33.83, respectively. Serial measurements in 3 patients with neuroblastoma receiving various therapies have revealed that there was a good correlation between urine NSE level and the response to therapy. These results indicate that NSE in urine may be a valuable marker for monitoring the effectiveness of therapy in patients with neuroblastoma.

Child, Preschool↗
PubMed1986

Biochemical improvement after treatment by bone marrow transplantation in I-cell disease.

The first case of successful bone marrow transplantation (BMT) in a patient with I-cell disease is reported. A 8-month-old girl with I-cell disease (N-acetylglucosaminylphosphotransferase deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched brother who has heterozygous level of the transferase activity. The following biochemical and clinical improvements have occurred: the transferase in peripheral lymphocytes increased to donor's level, and lymphocytic alpha-neuraminidase, beta-galactosidase and alpha-mannosidase increased to normal levels. Plasma acid hydrolase activities, which had been 10 to 60 times higher in the patient than normal control levels, have slowly but steadily decreased from one month after the graft. Such decreases were observed in the activities of alpha-mannosidase, N-acetyl-beta-glucosaminidase, alpha-fucosidase, arylsulfatase A and acidic beta-galactosidase. There was also a marked decrease of vacuolated peripheral lymphocyte after the BMT. Three-months after the engraftment, hepatomegaly gradually decreased in size, corneal clouding has not progressed, and tight skin seems to have improved.

Bone Marrow Transplantation↗
PubMed1986

N-sulphoconjugation of alicyclic, alkyl- and aryl-amines in vivo and in vitro.

Radioactive 35S in 3'-phosphoadenosine 5'-phosphosulphate was incorporated into alicyclic, alkyl- and aryl- amines in the presence of hepatic 105 000 g supernatants of female rats. 4-Phenylpiperazine, 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP), 1,2,3,4-tetrahydroisoquinoline, N-methylbenzylamine, desmethylzotepine and desmethylzimeldine showed the highest conjugation with 35SO3 among the amines tested. Incorporation of 35SO3 into alicyclic and alkyl-amines was higher at pH 10.0 than at pH 7.4 but the incorporation into arylamines was the opposite. A greater amount of 35SO3 was incorporated into the secondary alkylamines than the corresponding primary amines. Radioactive reaction products were identified as N-sulphoconjugates of amines by comparison on t.l.c. with synthetic authentic compounds. Reaction products of desmethylimipramine (DMI) and PTHP in vitro were isolated as their sulphoconjugates, identified by comparison of field desorption mass spectra, u.v. spectra, retention time on h.p.l.c. and RF values on t.l.c. with synthetic standards. DMI N-sulphonate and PTHP N-sulphonate were detected in the body of female rats treated orally with DMI and PTHP, respectively. These results indicate that N-sulphoconjugation is a common metabolic pathway of alicyclic, alkyl- and aryl-amines in vivo and in vitro.

Adenine Nucleotides↗
PubMed1986

Age- and sex-related changes in amine sulphoconjugations in Sprague-Dawley strain rats. Comparison with phenol and alcohol sulphoconjugations.

Age- and sex-related changes in sulphoconjugation were investigated in hepatic 105 000 g supernatants of three-week-old (young), seven-week-old (young adult), one-year-old (middle-aged) and two-year-old (old) Sprague-Dawley rats in the presence of biologically active sulphate. The supernatants of seven-week-old, one-year-old and two-year-old female rats catalysed the sulphoconjugations of alcohol (tiaramide as substrate), and alicyclic amine, alkylamine and arylamine more rapidly than those of the respective males, but the supernatants of three-week-old rats did not exhibit significant sex-related differences. The sulphoconjugations by the supernatants of female rats were substantially constant during ageing. On the other hand, the supernatants of seven-week-old male rats catalysed phenol (beta-naphthol as substrate) sulphoconjugation more rapidly than those of seven-week-old females, but the supernatants of two-year-old rats did not exhibit this sex-related difference. These results indicate that the substrates for sulphoconjugation could be divided into at least two groups: an alcohol and amine type, and a phenol type.

Age Factors↗
PubMed1986

[A study on the penetration of imipenem/cilastatin sodium into the female genital tissues].

A new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), was administered by intravenous drip infusion at a dose level of 500 mg/500 mg to 30 patients who underwent total abdominal hysterectomy for uterine myomas with or without benign ovarian tumors. The uterine arteries were clamped bilaterally at 0.25, 0.5, 1, 2, 3, 4, 6 and 8 hours after administration, and plasma samples and uterine tissues were taken for measurements of MK-0787 by bioassay and MK-0791 by HPLC. The measured values were analyzed using a two-compartment open model. Maximum concentrations of MK-0787 at 0.5 hour after the start of intravenous drip infusion were 98.5 micrograms/ml in the antecubital vein, 100.1 micrograms/ml in the uterine artery, 26.5 micrograms/g in the oviduct, 21.2 micrograms/g in the ovary, 19.1 micrograms/g in the endometrium, 19.0 micrograms/g in the myometrium, 22.1 micrograms/g in the cervix uteri and 16.4 micrograms/g in the portio vaginalis. These results suggest that the penetration of MK-0787/MK-0791 into female genital tissues is good, and sufficient concentrations are obtained enough to inhibit organisms which are frequently isolated from patients with pelvic inflammatory disease.

Adnexa Uteri↗
PubMed1985

Biochemical study in 28 children with lactic acidosis, in relation to Leigh's encephalomyelopathy.

An enzymatic study of cultured skin fibroblasts was made in 28 patients with lactic acidosis. In three of these patients a diagnosis of Leigh's encephalomyelopathy was established from autopsy findings. Pyruvate decarboxylase (PDC) deficiency was found in four patients. In two of them, in whom Leigh's encephalomyelopathy was proved by autopsy, PDC activity was lower than 10% of the normal. The other two living patients, who showed 22%-25% of the normal activity, had clinical symptoms and courses different from Leigh's disease. These findings suggest that the patients with severe PDC deficiency develop Leigh's disease but those with mild deficiency may not. A deficiency of cytochrome c oxidase was found in two siblings. One of them, who was diagnosed as having Leigh's encephalomyelopathy by postmortem examination, showed a reduction of cytochrome c oxidase in the liver and brain. In the other sibling, who is living, the reduction of cytochrome c oxidase was demonstrated in the cultured skin fibroblasts and biopsied muscle. In an electron-microscopic study of biopsied muscle, two patients with mitochondrial myopathy were found. Their fundamental enzymatic defects were unclear. In two patients, in whom Leigh's disease was suspected following a brain CT, the production of 14CO2 from [3-14C] pyruvate was found to be low; suggesting a reduced activity of the TCA cycle. In another 18 patients, the fundamental defect was not clear.

Acidosis↗
PubMed1985

Successful transplantation of soy bean agglutinin-fractionated, histoincompatible, maternal marrow in a patient with severe combined immunodeficiency and BCG infection.

A successful transplantation of soybean agglutinin (SBA) and sheep red blood cell (SRBC)-fractionated, maternal marrow in a patient with severe combined immunodeficiency (SCID) is reported. The engraftment of HLA-haplotype mismatched marrow cells was obtained without apparent graft versus host disease (GVHD). With immunological reconstitution the patient recovered from a BCG infection, which might have been caused by a BCG inoculation before his bone marrow transplantation.

Adult↗
PubMed1985

Serum bile acids and their conjugates in breast-fed infants with prolonged jaundice.

Serum bile acids and their conjugates were analysed in 20 breast-fed infants with prolonged jaundice. The mean total bile acid levels in serum were increased in the breast-fed infants with jaundice, as compared with those in either breast- or bottle-fed infants without jaundice. However, there were no significant differences between the groups. All the breast-fed infants examined, regardless of association with jaundice, had a bile acid pattern dominated by taurine conjugates (the ratio of glycine- to taurine-conjugated bile acid, G/T ratio, less than 1.00). In contrast, the bottle-fed infants without jaundice had a pattern dominated by glycine conjugates (G/T ratio, more than 1.00). Among the breast-fed infants with jaundice, the mean G/T ratio in those who had serum bilirubin levels over 10 mg/100 ml was significantly lower than that in those who had serum bilirubin levels of less than 10 mg/100 ml. The altered bile acid metabolism might be associated with the pathology of breast milk jaundice.

Bile Acids and Salts↗
PubMed1985

Glycogen storage disease type IB: a new model of genetic disorders involving the transport system of intracellular membrane.

Our studies have revealed that the primary lesion of GSD type Ib exists in the G6P transport system in the microsomal membrane. Distinct evidence for the existence of a specific G6P transport system in microsomal membrane was obtained through these studies. This is the first example of a genetic disorder involving the transport system of an intracellular membrane. HHH syndrome (hyperornithinemia, hyperammonemia, and homocitrullinuria), in which the transport of ornithine to the mitochondria is presumed to be defective, may be another example belonging to this category of genetic disorders (18-20). A possibility exists that there are many other disorders due to defects in the membrane transport of intracellular organelles.

Adult↗
PubMed1985

Isolation and characterization of a blood group active glycopeptide from porcine aorta.

A fucose-rich glycopeptide was prepared from the pronase digest of porcine thoracic aorta by gel-filtration through Sephadex G-100, DEAE-Sephadex A-25 column chromatography and alpha-amylase digestion. This glycopeptide was electrophoretically homogeneous. The large molecular size and chemical composition suggested that this glycopeptide was derived from mucin-type glycoprotein. The results of the beta-elimination reaction indicated that this glycopeptide contained the O-glycosidic linkages between galactosamine and serine/threonine. This glycopeptide exhibited blood group A and H activities. The present study revealed that the porcine thoracic aorta contains a blood group antigen of mucin-type glycoprotein nature.

Animals↗