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Biomedical subjects

T Nakai

Publications and source records attributed to T Nakai.

At least 19 recordsLinked to original sources
PubMed1992

Different antigenic nature in apparently healthy women with high serum CA 125 levels compared with typical patients with ovarian cancer.

BACKGROUND: CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. METHODS: Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OCI25-coated or 145-9-coated beads. RESULTS: The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125-labeled OC125 with OC125-coated beads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. CONCLUSIONS: Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values.

Acrylic Resins↗
PubMed1992

Microtubule-independent choleresis and anti-cholestatic action of tauroursodeoxycholate in colchicine-treated rat liver.

In order to cast light on the anti-cholestatic and cytoprotective properties of ursodeoxycholic acid (UDCA), intrahepatic transport and secretion of bile salts and biliary phospholipids were investigated by using isolated perfused livers from colchicine-pretreated rats. Administration of taurocholic acid (TCA) after colchicine pretreatment induced marked cholestasis. Tauroursodeoxycholic acid (TUDCA) treatment, in contrast, was associated with maintenance of bile flow, with excretion rates of bile acids and phospholipids similar to those in control animals. Furthermore, TCA-induced cholestasis in colchicine-treated rat livers was clearly decreased by co-administration of TUDCA. Although simultaneous addition of UDCA also showed slight improvement, with or without taurine pre-treatment, biliary bile-salt analysis also showed that cholestasis was markedly remitted as the excretion of taurine-conjugated UDCA was increased. The results suggest that the cytoprotective and anti-cholestatic effects of TUDCA may be linked to action at the intrahepatocyte level, represented by mild detergent effects on organelle lipids and preservation of intracellular transport even under microtubule-dysfunctional conditions. In addition, it was indicated that cytoprotective effects of UDCA may also be exerted after its conjugation with taurine inside hepatocytes.

Animals↗
PubMed1992

Glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels linked to activation of protein kinase C in vascular smooth muscle cells.

To clarify whether protein kinase is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells, we investigated the effects of protein kinase inhibitors on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding in A7r5 cells. Protein kinase C inhibitors (staurosporine and UCN-01) abolished the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding. In contrast, KT5720 and KT5823, which are more specific inhibitors of cAMP-dependent protein kinase and cGMP-dependent protein kinase, respectively, did not affect the effects of dexamethasone. Treatment with 100 nM dexamethasone for 48 hours increased protein kinase C activity in A7r5 cells. These results suggest that glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels, linked to activation of protein kinase C in vascular smooth muscle cells.

Alkaloids↗
PubMed1992

Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.

A cDNA that expresses a receptor for very low density lipoprotein (VLDL) was isolated from a rabbit heart cDNA library and characterized. The deduced amino acid sequence of the cDNA revealed that the cDNA encodes a protein with striking homology to the low density lipoprotein (LDL) receptor. Like the LDL receptor, the mature protein consists of the following five domains spanning 846 amino acids: 328 N-terminal amino acids including an 8-fold repeat of 40 amino acids homologous to the ligand binding repeat of the LDL receptor; 396 amino acid residues homologous to the epidermal growth factor precursor including three cysteine-rich repeats; a region immediately outside of the plasma membrane rich in serines and threonines; 22 amino acids traversing the plasma membrane; and 54 amino acids including the NPVY sequence that is required for clustering of the LDL receptor in coated pits and that projects into the cytoplasm. LDL-receptor-deficient Chinese hamster ovary cells transfected with the cDNA bound and internalized VLDL, beta-migrating VLDL, and intermediate density lipoprotein but did not bind LDL with high affinity. The 3.6- and 9.5-kilobase mRNAs for the VLDL receptor are highly abundant in heart, muscle, and adipose tissue. Barely detectable amounts of the mRNAs were present in liver. Based on the structural features, ligand specificity, and tissue expression of the mRNAs, we suggest that this VLDL receptor may mediate uptake of apolipoprotein E-containing lipoproteins enriched with triglyceride in nonhepatic tissues that are active in fatty acid metabolism.

Amino Acid Sequence↗
PubMed1992

The three-dimensional structure of guanine-specific ribonuclease F1 in solution determined by NMR spectroscopy and distance geometry.

Two-dimensional 1H-NMR studies have been performed on ribonuclease F1 (RNase F1), which contains 106 amino acid residues. Sequence-specific resonance assignments were accomplished for the backbone protons of 99 amino acid residues and for most of their side-chain protons. The three-dimensional structures were constructed on the basis of 820 interproton-distance restraints derived from NOE, 64 distance restraints for 32 hydrogen bonds and 33 phi torsion-angle restraints. A total of 40 structures were obtained by distance geometry and simulated-annealing calculations. The average root-mean-square deviation (residues 1-106) between the 40 converged structures and the mean structure obtained by averaging their coordinates was 0.116 +/- 0.018 nm for the backbone atoms and 0.182 +/- 0.015 nm for all atoms including the hydrogen atoms. RNase F1 was determined to be an alpha/beta-type protein. A well-defined structure constitutes the core region, which consists of a small N-terminal beta-sheet (beta 1, beta 2) and a central five-stranded beta-sheet (beta 3-beta 7) packed on a long helix. The structure of RNase F1 has been compared with that of RNase T1, which was determined by X-ray crystallography. Both belong to the same family of microbial ribonucleases. The polypeptide backbone fold of RNase F1 is basically identical to that of RNase T1. The conformation-dependent chemical shifts of the C alpha protons are well conserved between RNase F1 and RNase T1. The residues implicated in catalysis are all located on the central beta-sheet in a geometry similar to that of RNase T1.

Amino Acid Sequence↗
PubMed1992

Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core.

The DNA-binding domain of the c-myb protooncogene product consists of three imperfect tandem repeats of 51 or 52 amino acids, each of which contains three conserved tryptophans, spaced 18 or 19 amino acids apart. The structure of the third repeat, which is essential for sequence-specific DNA binding, has been determined by NMR with distance geometry calculation. It includes three well-defined helices (residues 149-162, 166-172, and 178-187) maintained by a hydrophobic core that includes the three conserved tryptophans, together with two histidines. Helices 2 and 3 form a structure related to but distinct from a canonical helix-turn-helix motif. In particular, the turn between these helices is one amino acid longer than the corresponding turn in bacterial repressors and homeodomains and contains a proline residue. In addition, the architecture of the three helices is different from those of homeodomains and DNA-binding domains of bacterial repressors. Based on the present structure, the binding mode of Myb repeat 3 with a specific DNA is also discussed.

Amino Acid Sequence↗
PubMed1992

Effect of cavity-modulating mutations on the stability of Escherichia coli ribonuclease HI.

The size of the cavity around Ser68 of Escherichia coli ribonuclease HI was modulated by amino acid substitutions to examine the effects on the stability of the enzyme. Five mutant proteins, Ser68----Gly, Ser68----Ala, Ser68----Thr, Ser68----Val and Ser68----Leu, were constructed. Each of the mutant proteins exhibited at least 40% of the enzyme activity of the wild-type protein. The stabilities of the mutant proteins were determined from urea-denaturation and thermal-denaturation curves. Among the five mutations, only the Ser----Val mutation resulted in an increase in the stability of the enzyme. The melting temperature, tm, at pH 3.0 of the mutant protein Ser68----Val was increased by 1.9 degrees C. Its free-energy change of unfolding in the absence of urea, delta G(H2O), and the midpoint of the denaturation curve, [D]1/2, were also increased by 5.4 kJ/mol and 0.18 M, respectively. The increase in the stability of the enzyme is probably due to the filling of the cavity space around Ser68 by valine. However, the mutation of Ser68 to glycine or leucine residues resulted in a considerable decrease in stability. In these cases, some conformational changes occur, as suggested by the CD and 1H-NMR spectra of these mutant proteins.

Base Sequence↗
PubMed1992

Bordetella bronchiseptica dermonecrotizing toxin suppresses in vivo antibody responses in mice.

The effects of Bordetella bronchiseptica dermonecrotic toxin (DNT) on the in vivo antibody response of mice were investigated. Intravenous injection of DNT at doses of 0.5 and 2.0 ng resulted in a significant suppression of the antibody response both to sheep red blood cells and to Escherichia coli lipopolysaccharide as measured by plaque-forming cell and hemagglutination assays. Spleen weights of mice given the same doses of DNT were significantly reduced, while the weights of thymuses and mesenteric lymph nodes were not. Numbers of Thy-1,2+ T lymphocytes, L3T4+ T lymphocytes, Lyt-2+ T lymphocytes and surface-immunoglobulin-positive lymphocytes decreased in spleens of the DNT-treated mice. Since the ratio of each lymphocyte population to the total number of splenic lymphocytes was not significantly different between the DNT-treated and non-treated mice, it is unlikely that DNT has a cytotoxic activity or a mitogen activity to some specific population of lymphocytes. Thus, we considered that the immunosuppression was attributable to a dysfunction of the spleen atrophied by the DNT.

Animals↗
PubMed1992

Papaverine inhibits transcytotic vesicle transport and lipid excretion into bile in isolated perfused rat liver.

Papaverine is a nonspecific smooth muscle relaxant and a phosphodiesterase inhibitor. Its effects on biliary excretion of lipids and horseradish peroxidase were investigated in a single-pass isolated perfused rat liver model. A constant infusion of papaverine (1.6 mumol/min; 40 mumol/L) significantly increased bile flow (microliters per minute per gram of liver) before (2.03 +/- 0.09 vs. 1.0 +/- 0.06) and after sodium taurocholate infusion (2.77 +/- 0.10 vs. 1.88 +/- 0.11). However, papaverine significantly and reversibly reduced biliary excretion of phospholipids and cholesterol (nanomoles per minute per gram of liver) after a 1.0 mumol/min sodium taurocholate infusion, from 7.45 +/- 0.83 and 1.42 +/- 0.15 to 1.75 +/- 0.18 and 0.39 +/- 0.06, respectively (p less than 0.01), whereas secretion of bile acids was unaffected. When a 1-min pulse of horseradish peroxidase (25 mg) was infused in isolated perfused rat liver after a continuous infusion of N6,O-2'-dibutyryladenosine 3',5'-cyclic monophosphate (0.25 mumol/min; 6.25 mumol/L), horseradish peroxidase appeared in bile in an early (4 to 6 min) and late (20 to 25 min) peak. Papaverine significantly reduced the late peak, from 1.211 +/- 0.264 to 0.498 +/- 0.107 (p less than 0.01). Papaverine had no significant effects on either cyclic AMP or cyclic GMP in the liver and bile, although it has been reported that papaverine is a phosphodiesterase inhibitor. These findings indicate that papaverine inhibits biliary excretion of lipids but not bile acids, and they suggest that papaverine has an inhibitory effect on transcytotic vesicle transport independent of an increase of cyclic nucleotides in hepatocytes.

Animals↗
PubMed1992

Tauro-beta-muricholate preserves choleresis and prevents taurocholate-induced cholestasis in colchicine-treated rat liver.

In recent clinical and animal experimental studies, ursodeoxycholic acid (UDCA) has been noted to have marked choleretic and cytoprotective actions. To define the mechanism and determine whether such favorable influence is specific to UDCA, the choleretic action of beta-muricholic acid (beta-MCA), which has a similar chemical structure, was studied using an isolated rat-liver-perfusion system. As a result, beta-MCA and taurine-conjugated beta-MCA (T beta-MCA) stimulated bile flow accompanied by elevation of bile acid output and phospholipid output, and beta-MCA caused an elevation in biliary HCO3- concentration in normal rat livers. After colchicine treatment, taurocholic acid (TCA) administration was associated with marked cholestasis while both beta-MCA and T beta-MCA still increased bile flow under the same conditions. Furthermore, simultaneous administration of beta-MCA or, more markedly, T beta-MCA reversed the effects of TCA alone in colchicine-treated rat liver; significant preventive effects against the cholestasis could be shown. These data suggest that beta-MCA and especially T beta-MCA can support choleresis even under conditions of colchicine-dependent microtubule dysfunction. The effects of T beta-MCA on organelle lipids and their intracellular transport may differ from those of TCA, presumably because of the anticholestatic and cytoprotective effects of T beta-MCA.

Animals↗
PubMed1992

Properties of a new virus belonging to nodaviridae found in larval striped jack (Pseudocaranx dentex) with nervous necrosis.

Spherical virus particles were purified from larval striped jack (Pseudocaranx dentex) with nervous necrosis. The virus consists of nonenveloped particles, about 25 nm in diameter, and contains two single-stranded, positive-sense RNA molecules with molecular weights of 1.01 x 10(6)Da (RNA 1) and 0.49 x 10(6)Da (RNA 2), respectively. The RNAs do not have poly(A) sequences at the 3' terminus. Virus structural proteins consist of two proteins with molecular weights of 42 and 40 kDa. When translated into cell-free extracts of rabbit reticulocytes, RNA 1 directed the synthesis of the 1a protein (100 kDa), whereas RNA 2 synthesized the 2a protein (42 kDa), which is probably the coat protein of the virus, and a polypeptide of 40 kDa which appears to be the processed form of the 42-kDa protein. Under electron microscopic observation, the virus particles were found in the tissues of the central nervous system of the affected larval striped jack. From morphological and biochemical properties of the virus, we identified this virus as a new member of the family of Nodaviridae and designated it striped jack nervous necrosis virus.

Animals↗
PubMed1992

Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA).

Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled MoAbs including IgG, Fab or human/mouse chimeric Abs. Immune complexes composed of HAMA and MoAbs were formed. The percentage of radioactivity with a high molecular weight was related to HAMA levels determined by enzyme linked immunosorbent assay. Most radioactivity present in immune complex shifted to the antibody fraction after the addition of normal murine serum. All of seven sera were reactive with all four murine IgGs and this suggests that HAMA in these patients recognised the constant region of MoAbs. In one patient, HAMA was considered to recognise the variable region and to be anti-idiotypic. There was no significant binding with human/mouse chimeric Abs in any HAMA positive serum, although five out of seven patients were reactive with murine MoAb Fab, indicating that HAMA was composed of Abs responsive to the CH1 or CL region of murine IgG. These results suggest that (1) HAMA was composed of Ab responsive to Fc portion and/or CH1 or CL region of murine IgG, and (2) human/mouse chimeric Abs look promising in the repeated infusion of MoAb in HAMA positive patients.

Aged↗
PubMed1992

Effects of probucol on impaired cardiac performance and lipid metabolism in streptozotocin-induced diabetic rats.

Plasma lipids and cardiac performance were studied in diabetic rats treated with probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to probucol-treated or untreated groups. The rats in the two probucol-treated groups (control- and diabetic-probucol groups) were fed a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then cardiac performance was assessed by the isolated perfused working heart technique. Probucol treatment had no effect on the cardiac performance of the nondiabetic control rats. The peak left ventricular developed pressure and maximum rate of change in left ventricular pressure during systole were significantly greater in the probucol-treated diabetic rats than in the untreated diabetic rats (p less than 0.05), although cardiac performance did not improve to the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and phospholipid were significantly elevated in the untreated diabetic rats, and probucol treatment decreased significantly the plasma cholesterol and free fatty acid concentrations (p less than 0.05). These data suggest that probucol treatment improves plasma lipids and cardiac performance in rats with experimental diabetes and may prevent diabetic cardiomyopathy.

Animals↗
PubMed1992

Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture.

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

An epidemiological study on hyponatremia in psychiatric patients in mental hospitals in Nara Prefecture.

Hyponatremia occurs often in mental illness. The frequency was not noticed because of the uncharacteristic symptoms of mild hyponatremia. Of the 1,114 psychiatric inpatients retrospectively surveyed, 10.5% had hyponatremia. Not only patients with schizophrenia, but also patients with other mental illness, especially with epilepsy, having hyponatremia were confirmed. An early onset, a long duration of psychiatric disorder and a prolonged admission were statistically significant factors. Nicotine abuse was not a significant factor. It was suggested that the pathogenesis of hyponatremia in psychiatric patients might be involved in a chronic course of psychiatric disorders and poor response to psychopharmacotherapy.

Adult↗