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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 415 records · Page 23Linked to original sources
PubMed1995

[Persistent discrepancy between FDP and D-dimer in a patient with acute leukemia].

In a patient with acute myeloblastic leukemia, serum fibrinogen/fibrin degradation products (FDP) were markedly elevated to 54.91 micrograms/ml, but plasma D-dimer was only slightly elevated (1.44 micrograms/ml). FDP in plasma measured by a method using monoclonal antibody specific to FDP was less than 5 micrograms/ml. Gradual reduction of blastic cells was obtained with the therapy of low-dose cytarabine, G-CSF and etoposide. The serum FDP increased up to 71.74 micrograms/ml accompanied with a transient elevation of D-dimer, and subsequently declined without any anticoagulant therapy. However, a discrepancy between serum FDP and plasma D-dimer lasted for a long time. In this case persistent acceleration of coagulation and fibrinolysis which may result in the elevation of serum FDP was not observed, suggesting that the greater part of increased FDP didn't reflect the true FDP formed by plasmin. There were possibilities that elevated serum FDP values were also caused by the presence of soluble fibrin, unclottable fibrinogen and the degradation products by nonplasmic proteinases. Simultaneous measurements of FDP and D-dimer are useful for a more accurate evaluation of hyperfibrinolytic states and to avoid possible misinterpretations due to falsely positive FDP.

Aged↗
PubMed1994

Decidua is a possible source of serum mouse soluble interleukin-6 receptor (msIL-6R): gestational profile of serum msIL-6R concentration.

The serum concentration of msIL-6R of 10 weeks old virgin ICR mouse assessed by a RIA was 45.6 +/- 6.6 ng/ml. The serum msIL-6R concentration of the pregnant mouse mated at 10 weeks of age was 41.2 +/- 3.0 ng/ml on day 7 of pregnancy. The serum concentration gradually increased during gestation and reached peak on day 17 of pregnancy (149.1 +/- 13.7 ng/ml). On the third day of the puerperium, the serum msIL-6R concentration of the mother from which the pups had been removed on the day of delivery was decreased to the level of that on day 7 of pregnancy. IL-6R mRNA level in the decidua significantly increased during mid and late gestational stages. msIL-6R was detected in the medium of cultured decidual cells (8.03 +/- 0.28 ng/ml), but not placental cells. Western analysis for msIL-6R using the conditioned medium of the cultured decidual cells resulted in a single band at approximately 45 K. To find out a biological role of msIL-6R during gestation, placental cells were incubated with mIL-6 and msIL-6R, and mPL-I concentration in the medium was assessed by RIA. 2.5 nM mIL-6 did not affect the secretion of mPL-I in placental cells; however, addition of msIL-6R resulted in a significant stimulation of mPL-I secretion. These results suggest that serum msIL-6R, which is likely to be secreted from decidua, may play an important role during gestation.

Analysis of Variance↗
PubMed1994

Unsaturated fatty acids are required for continuous proliferation of transformed androgen-dependent cells by fibroblast growth factor family proteins.

Increase in dietary fat intake has been reported to be associated with progression of hormone-dependent cancers. To explore its mechanism, we examined the effects of fatty acids on the growth of androgen-dependent SC-3 cells cloned from mouse mammary cancer (Shionogi carcinoma 115). Their androgen-dependent growth was potentiated by linoleic acid in the defined medium. The effect of linoleic acid on fibroblast growth factor (FGF)-dependent growth was also addressed because androgen had been demonstrated to exert its mitogenic activity on SC-3 cells through an induction of the unique FGF family protein termed as androgen-induced growth factor. Exposure of SC-3 cells to basic FGF or androgen-induced growth factor exhibited only transient growth response. However, simultaneous addition of linoleic acid to the medium sustained the proliferation of FGF-stimulated, but not FGF-unstimulated, cells, although linoleic acid did not exert the significant effect on the process of S-phase entry of basic FGF-stimulated cells. Palmitoleic acid and oleic acid appeared to exert the actions similar to linoleic acid, while stearic acid was without any effect. Neither cyclooxygenase inhibitor nor 5-lipoxygenase inhibitor could block the growth-promoting ability of linoleic acid. Linoleic acid also enhanced their anchorage-independent growth in the presence of basic FGF. These results indicate that these unsaturated fatty acids play a role in sustaining the proliferation of FGF-stimulated SC-3 cells.

Animals↗
PubMed1994

Developmental changes of nerve growth factor levels in the gracile axonal dystrophy mouse.

Nerve growth factor (NGF) levels were measured in various tissues of the gracile axonal dystrophy (GAD) mouse. When the disease had fully progressed, the NGF levels in the skeletal muscle, dorsal root ganglion and the spinal cord were decreased. These findings suggest that a reduction of the NGF level is involved in the pathophysiological processes in the GAD mouse.

Animals↗
PubMed1994

Enzymic O-sulfation of tyrosine residues in hirudins by sulfotransferase from Eubacterium A-44.

The enzymic O-sulfation of Tyr residues in a recombinant hirudin variant-1 (rHV-1) and its analog in which Glu61 and Glu62 were replaced by Tyr, [E61Y, E62Y]rHV-1, was carried out by use of sulfotransferase isolated from an anaerobic bacterium from the human intestine, Eubacterium A-44. Although rHV-1 was not sulfated by this enzyme, the sulfation of [E61Y, E62Y]rHV-1 was observed, and three kinds of sulfated analog, whose C-terminal six amino acid residues were -PYY(SO3H)YLQ, -PYYY(SO3H)LQ, and -PYY(SO3H)Y(SO3H)LQ, were obtained. Among the sulfated hirudin analogs tested here, the Tyr62 and Tyr63 bisulfated [E61Y, E62Y]rHV-1 showed the strongest thrombin inhibition with the inhibition constant (Ki) of 0.0430 pM, followed by the Tyr63 monosulfated analog (Ki = 0.0593 pM) and the Tyr62 monosulfated one (Ki = 0.158 pM). The Tyr63 monosulfated analog and Tyr62 and Tyr63 bisulfated one were more potent inhibitors of thrombin than unsulfated rHV-1. The increase in affinity caused by sulfation was predominantly due to an increase in the association-rate constant.

Amino Acid Sequence↗
PubMed1994

A deletion in the second cytoplasmic loop of GluR3 produces a dominant negative mutant of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor.

We have characterized a GluR3 mutant (sGluR3) which has a 33-amino acid deletion in its second cytoplasmic loop (deficit from Tyr-715 to Gly-747 of GluR3-flop). Xenopus oocytes injected with cRNA transcribed from cDNA for this mutant did not respond to kainate and glutamate (each 100 microM) at a holding potential of -70 mV. In oocytes coinjected with cRNAs for this mutant and for normal alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits, the current response to both kainate and glutamate was much weaker than that observed in oocytes injected with cRNA for the normal subunits alone. This inhibitory action was not accompanied by a significant change of ED50 value and shape of the I-V curve and was AMPA receptor-specific. A comparable deletion in GluR1 produced a mutant with properties similar to those of sGluR3, while a 33-amino acid deletion elsewhere in the second cytoplasmic loop of GluR3 (Met-674 to Phe-706) gave a mutant with a weaker effect. These results suggest that sGluR3 acts as a dominant negative mutant on the functional expression of normal AMPA receptors in oocytes by assembling with the normal subunits to produce an essentially nonfunctional receptor complex.

Amino Acid Sequence↗
PubMed1994

Ataxia-ameliorating effects of YM-14673, a potent analog of thyrotropin releasing hormone, in ataxic mutant mice.

The effects of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]- L-histidyl-L-prolinamide dihydrate), a potent analog of thyrotropin releasing hormone (TRH), on the behavior of ataxic mutant mice (staggerer, realer, Purkinje cell degeneration and weaver mice) were investigated in comparison with those of TRH in an open-field apparatus. The fall index, the ratio of the number of falls to the distance moved, was defined as an index for ataxia. YM-14673 reduced the fall index in all types of ataxic mice examined and was more potent than TRH in reeler, staggerer and Purkinje cell degereration mice. YM-14673 may have a beneficial effect on patients with spinocerebellar degeneration.

Animals↗
PubMed1994

The synthesis of a pyridyl analog of adenosylcobalamin and its coenzymic function in the diol dehydratase reaction.

A novel analog of adenosylcobalamin in which 5,6-dimethylbenzimidazole and D-ribose moieties of the nucleotide loop are replaced by pyridine and the trimethylene group, respectively, was synthesized and examined for coenzymic function. The coordination of pyridine to the cobalt atom in this analog was stronger than that of 5,6-dimethylbenzimidazole in the corresponding homolog. The adenosyl form of pyridyl analog served as partially active coenzyme for diol dehydratase. The kcat/Km values calculated from the initial velocity indicate that this analog is a better coenzyme than the 5,6-dimethylbenzimidazolyl or imidazolyl counterpart. However, the reaction with the pyridyl analog as coenzyme was accompanied with a concomitant inactivation during catalysis, with a kcat/Kinact value 50-100 times lower than that for adenosylcobalamin or the 5,6-dimethylbenzimidazolyl analog. Therefore, it can be concluded that the 5,6-dimethylbenzimidazole moiety of adenosylcobalamin is important for continuous progress of a catalytic cycle by protecting the reactive intermediates from side reactions.

Benzimidazoles↗
PubMed1994

Localization of rabphilin-3A, a putative target protein for Rab3A, at the sites of Ca(2+)-dependent exocytosis in PC12 cells.

Rab3A/Smg 25A, a small GTP-binding protein, is highly concentrated in presynapse of neurons and implicated in neurotransmitter release. We have recently identified a putative target protein for Rab3A, isolated its cDNA, and designated it as Rabphilin-3A. To examine whether Rabphilin-3A as well as Rab3A is localized at the sites of Ca(2+)-dependent exocytosis, we investigated here localization of Rabphilin-3A and Rab3A in comparison with the sites of exocytosis in the differentiated PC12 cells. Rabphilin-3A as well as Rab3A was highly concentrated at the tips of the neurites where Ca(2+)-dependent exocytosis took place. Inversely, neither Rabphilin-3A nor Rab3A was concentrated at the tips of the neurites where Ca(2+)-dependent exocytosis did not take place. These results suggest that Rabphilin-3A as well as Rab3A constitutes a part of the machinery necessary for neurotransmitter release.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, in the rat middle cerebral artery occlusion model.

The aim of this study was to evaluate the effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, on ischaemic brain tissue damage using the rat middle cerebral artery occlusion model. Under anaesthesia, the left middle cerebral artery was exposed without cutting the dura mater via a subtemporal craniotomy, under an operating microscope. Photo-illumination (wave length; 540 nm) was applied to the middle cerebral artery and then rose bengal (20 mg/kg) was administered intravenously. The middle cerebral artery was completely occluded by thrombus about 6 min after the administration of rose bengal. U74006F (1.0 mg/kg) was then injected intravenously just after the cessation of illumination. Twenty four hours after the operation, the extent of ischaemic damage was measured by magnetic resonance imaging technique. After measuring the extent of ischaemic damage, the brain was immediately removed from animals treated with or without U74006F for determination of lipid peroxidation, and the generation of free arachidonic acid in the brain. U74006F significantly (P < 0.01) reduced the size of ischaemic damage. Twenty-four hours after the operation, lipid peroxidation and the concentration of free arachidonic acid in the left hemisphere (infarction side) were significantly (P < 0.05) higher than in the right hemisphere. U74006F significantly (P < 0.05) decreased the content of lipid peroxidation products and free arachidonic acid. There was a significant (P < 0.05) correlation between the extent of ischaemic damage and the concentration of lipid peroxidation products in the left hemisphere 24 h after the operation. In conclusion, U74006F might reduce the extent of ischaemic damage by inhibiting lipid peroxidation in the brain, thus minimizing oxidative damage to neural tissues.

Animals↗
PubMed1994

Tissue factor in plasma of patients with disseminated intravascular coagulation.

Recently it has been shown that tissue factor (TF), an important trigger for initiating blood coagulation, is present in the circulating plasma. In order to assess the clinical implications of TF in plasma, plasma concentration of TF was quantitated in 65 patients with disseminated intravascular coagulation (DIC). The mean concentration of plasma TF was elevated in patients with DIC at presentation as compared with healthy subjects (446 +/- SD 536 pg/ml vs. 138 +/- 51 pg/ml, P < 0.001). Abnormally high levels were found only in 46.2% of the patients, predominantly in patients with non-hematological solid tumors and acute leukemia. Plasma TF did not correlate with hemostatic markers of DIC such as thrombin-antithrombin III complex, prothrombin fragment 1 + 2, plasma-alpha 2-plasmin inhibitor complex, FDP, D-dimer, or fibrinogen. Serial determinations of plasma TF demonstrated that plasma TF changes roughly in parallel with the course of DIC in most patients with elevated TF at presentation of DIC. These findings suggest that plasma TF is potentially valuable for monitoring the progress of DIC in a limited population of patients.

Disseminated Intravascular Coagulation↗
PubMed1994

Collagen fibrils in the odontoblast layer of the rat incisor by scanning electron microscopy using the maceration method.

BACKGROUND: There is not universal agreement on the existence of the extracellular pathway from the pulp along the odontoblast layer to the predentin. METHOD: To confirm this pathway, the architecture of collagen fibrils in the rat incisor dentin and pulp, especially in the odontoblast layer of the lateral (periodontal ligament) sides of the tooth, was demonstrated in the present investigation using scanning electron microscopy of the maceration method for collagen networks. RESULTS: Numerous collagen bundles were observed in the odontoblast layer in the mature odontoblast region which, except for the young odontoblast region, comprises the major portion of the incisor. The collagen bundles went from the pulp, through the odontoblast layer, and were woven into the collagen network of the predentin. The meshwork structure was composed of fine secondary fibrils among these collagen bundles. The surface of the predentin contained many oval-shaped holes which were surrounded by collagen fibrils. Fracturing the dentin longitudinally relative to the dentinal tubules revealed that the arrangement of the collagen fibrils at the surface of the tubules was either circular or oblique. In the young odontoblast region, i.e., the thin portion from the apical end of the incisor where the mineralization of the dentin does not occur and where the height of the odontoblasts was less than 30 microns, many thick bundles composed of thick collagen fibrils ran straight from the pulp to the predentin through the odontoblast layer and fanned out in the collagen network of the predentin. These thick bundles might correspond to the so-called "von Korff fibers." The distribution of collagen fibrils in the pulp was random except on the surface of the blood vessels where the fibrils comprised two sheets of collagen: the inner sheet which coursed longitudinally to the long axis of the vessel, and the outer sheet which ran transversely. CONCLUSION: It was considered that the fluid in the pulp could flow to the predentin along the collagen fibrils through the tight junction between the odontoblasts.

Animals↗
PubMed1994

Copper(II)[2,3-butanedionebis(N4-methylthiosemicarbazone)], a stable superoxide dismutase-like copper complex with high membrane penetrability.

To obtain a superoxide dismutase (SOD)-like drug that could readily cross the cell membrane, we investigated the SOD-like activity, intracellular uptake, and stability of several Cu(II)Bisthiosemicarbazones (Cu(II)BTS). Among these Cu(II)BTS chelates, Cu(II)[2,3-Butanedionebis(N4-methylthiosemicarbazone)] (Cu(II)BMTS) was the most effective SOD-like compound with activity similar to activity reported for various previously reported SOD-like Cu complexes. Biodistribution studies in mice indicated that Cu(II)BMTS rapidly distributed to all tissues and readily crossed cell membranes as well as the blood-brain barrier with high distributions to the brain and the heart. Moreover, Cu(II)BMTS was stable in mouse brain homogenate and mouse blood. These results suggest that Cu(II)BMTS has the potential to be used as a SOD-like drug capable of reaching intracellular superoxide generating sites.

Animals↗
PubMed1994

The use of a human dura mater allograft for the repair of a contaminated abdominal wall defect: report of a case.

A case report of an infected full-thickness abdominal wall defect treated successfully with a human dura mater allograft is presented. A review of the literature and a discussion of prosthetic abdominal wall repair is also included. A 46-year-old woman presented with multiple small bowel perforations and a large abdominal wall defect due to a motor vehicle collision. A gamma-irradiated human dura mater prosthesis was used to repair the large abdominal wall defect which had been infected by a jejunal fistula. After more than 4 years of follow-up, the patient is free of complications, including wound infection, herniation, and ileus. The human dura mater allograft is thus considered to be a useful prosthesis for repairing potentially infected wounds.

Abdominal Muscles↗
PubMed1994

ADHD-related behavior among non-referred children: parents' ratings of DSM-III-R symptoms.

To identify the prevalence of ADHD symptoms among non-referred children, parents' ratings based on DSM-III-R criteria for ADHD were obtained for 1022 metropolitan children of ages 4 to 12. The prevalence rates of fourteen behavior items were markedly lower for boys of ages 10-12 than of ages 7-9, and for girls of ages 7-9 than of ages 4-6. 41.5% of the 7.7% subjects meeting ADHD criteria had been identified by their teachers as having problems symptomatic of ADHD, and one third had been reported by their parents as having conduct problems and emotional difficulties. A factor analysis revealed three factors: inattention; hyperactivity; and excessive verbal activities.

Attention Deficit Disorder with Hyperactivity↗