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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 631 records · Page 35Linked to original sources
PubMed1993

Differential effects of acyclothymidine, a potent pyrimidine nucleoside phosphorylase inhibitor, on the pharmacokinetics of doxifluridine in rabbits via oral administration.

Acyclothymidine (AcyT, 5-methyl-1-(2'-hydroxyethoxymethyl)uracil), a potent inhibitor of pyrimidine nucleoside phosphorylase (PyNPase), was co-administered with 5'-deoxy-5-fluorouridine (5'-DFUR), a PyNPase activating prodrug of 5-fluorouracil (5-FU), to rabbits. The absorption and pharmacokinetic parameters of 5'-DFUR and its active metabolite 5-FU, after administration of 5'-DFUR in combination with AcyT, were evaluated in the animals. Animals were given an oral or intravenous administration of 5'-DFUR (50 mg/kg) in combination with an equimolar dose of AcyT (40 mg/kg). The half-lives (t1/2) of 5'-DFUR and 5-FU in plasma were 16.8 and 11.5 min, respectively. AUC (area under the plasma concentration-time curve) of 5'-DFUR and 5-FU following the oral administration of 5'-DFUR (50 mg/kg) was 1710 and 24.3 micrograms.min/ml, respectively. After the oral co-administration of 5'-DFUR and AcyT (at a molar ratio of 1:1), the AUC values for 5'-DFUR and 5-FU increased to 2680 and to 121.1 micrograms.min/ml, respectively. However, this combination had little effect on the t1/2 of 5'-DFUR.

Administration, Oral↗
PubMed1993

Binding of lysozyme to synthetic monosaccharide lipid A analogue, GLA60.

Recent studies by our group suggested that lysozyme (LZM) has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A, well-known as sharing large part of lipid A activities but with very low toxicity. In this study, we characterized the interaction of LZM with GLA60 in comparison to that with E. coli 0111 LPS (smooth form), taking a physicochemical approach. Using a dansylated lysozyme probe (DNS-LZM), LZM was found to bind to GLA60 in all 3 of its forms, free acid, triethylamine (TEA) salt and bovine serum albumin (BSA) complex of GLA60, as well as natural LPS. Compared with LPS, the complex formation of the TEA salt was weakly dependent on temperature and incubation time. LZM also bound to biologically inactive GLA analogues, GLA 64 and GLA69, at a high affinity, as well as to GLA 60. By using chemically modified LZM, it was found that the ionic as well as hydrophobic interactions are important for the complex formation.

Chemical Phenomena↗
PubMed1993

Adsorption of mexiletine onto activated charcoal in macrogol-electrolyte solution.

Adsorption studies in vitro of mexiletine onto activated charcoal were performed in macrogol (polyethylene glycol)-electrolyte solution (PEG-ELS) and JP XII disintegration medium No. 2 (second medium). Mexiletine was adsorbed more extensively onto activated charcoal in PEG-ELS than that in JP XII second medium. The maximum adsorptive capacity of activated charcoal for the drug was 328 and 284 mg per gram of charcoal in PEG-ELS and JP XII second medium, respectively. In addition, the equilibrium constant of activated charcoal estimated according to the Langmuir equation was 0.079 and 0.034 l per gram of charcoal in PEG-ELS and JP XII second medium, respectively. Adsorption of mexiletine onto activated charcoal was decreased by omitting macrogol, sodium sulfate or sodium bicarbonate from a standard PEG-ELS formulation. Oral activated charcoal will be useful in combination with whole bowel irrigation with PEG-ELS in mexiletine overdose because of its excellent adsorbability in the solution.

Adsorption↗
PubMed1993

Effects of spiradoline mesylate, a selective kappa-opioid-receptor agonist, on the central dopamine system with relation to mouse locomotor activity and analgesia.

Neurochemical and behavioral investigations were made to assess the role of central dopaminergic systems in mouse locomotor activity and analgesia by spiradoline mesylate. Analgesic activities of the kappa-opioid-receptor agonists spiradoline and U-50488H were not altered by haloperidol or L-dopa, whereas morphine analgesia was enhanced by haloperidol but attenuated by L-dopa. Spiradoline decreased spontaneous locomotor activity in mice and inhibited methamphetamine- or morphine-induced locomotor activity. In contrast, morphine given alone increased locomotor activity and enhanced methamphetamine-induced locomotor activity. In a neurochemical study, spiradoline decreased the amounts of dopamine metabolites in the striatum, but did not alter them in the brainstem and cerebral cortex. Morphine increased the dopamine metabolite contents in all three brain regions tested. These results suggest that inhibition of the dopaminergic pathway in the brain by spiradoline may be involved in its suppression of locomotor activity, but not in its analgesia; whereas, stimulation of the dopaminergic pathway by morphine seems to function in both behaviors: enhancement of locomotor activity and inhibition of analgesia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Enzymatic synthesis of a novel trisaccharide, glucosyl lactoside.

Cyclomaltodextrin glucanotransferase from Bacillus stearothermophilus produced a series of oligosaccharides by the transglycosylation reaction with cyclomaltohexaose as a glycosyl donor and D-lactose as its acceptor. The content of oligosaccharide A as the main transfer product was 22.1% of the total sugar. The content was increased to 34.1% by hydrolysis with glucoamylase. Oligosaccharide A was isolated by column chromatography and crystallized. By chemical and enzymatic analyses, oligosaccharide A was found to be a novel non-reducing trisaccharide; O-beta-D-galactopyranosyl-(1-->4)-O- beta-D-glucopyranosyl alpha-D-glucopyranoside.

Carbohydrate Sequence↗
PubMed1993

Ca2+ sensitivity of skinned uterine muscle fibers in unilaterally pregnant rats.

We prepared chemically skinned uterine muscle fibers from both horns of unilaterally pregnant rats and investigated the effect of gestation on the Ca2+ sensitivity of the Ca(2)-induced contraction. The Ca2+ sensitivity was defined as the pCa (minus logarithm of free calcium concentration) required for half maximum activation of force production. Gravid horns did not show any statistical difference in the Ca2+ sensitivity between normal pregnant and unilaterally pregnant rats. Non-gravid horns of unilaterally pregnant rats before Day 14 of gestation showed the same behavior in the Ca2+ sensitivity as horns of normal pregnant rats. After Day 15 of gestation the Ca2+ sensitivity of non-gravid horn also increased but significantly less than that of gravid horn. Taking into account the hormonal situation, the present results suggest that some local factors, such as an increased size of conceptus (fetus and placenta) and/or intercellular binding conditions of myometrium modulated by the gap junction formation and the appearance of connexin molecules, may also be requisite for the regulation of the contractile activity associated with parturition and delivery of the fetus and placenta.

Animals↗
PubMed1993

Effects of bed rest on bone metabolism in patients with femoral neck fracture.

The effect of continuous 1 week bed rest during traction on bone metabolism were studied in patients with femoral neck fracture. Bone demineralization was assessed by measuring serum calcium (Ca), phosphorus (P), and alkaline phosphatase (AlkP) before, during, and after 1 week-bed rest with skeletal traction. In addition, 24-hour urinary excretion of calcium and phosphorus were measured. Serum Ca did not change significantly before, during, and after bed rest, whereas serum P increased after 1 week bed rest and postoperatively remained significantly elevated. Serum AlkP did not increase with bed rest, but became elevated postoperatively. Urinary Ca excretion increased from 105.8 +/- 15.2 to 138.0 +/- 15.4 mg/24h after 1 week of bed rest, and remained elevated postoperatively. In contrast, urinary P excretion initially increased 495.1 +/- 65.0 to 610.8 +/- 87.7 mg/24h, and subsequently decreased to a level significantly less than the admission level. These results suggest that 1 week bed rest for the patients with femoral neck fracture resulted in bone atrophy and demineralization.

Aged↗
PubMed1993

Primary pulmonary B-cell lymphoma diagnosed by kappa-lambda imaging of broncho-alveolar lavage fluid lymphocytes.

A 69-year-old woman was examined due to abnormal pulmonary shadows on her chest roentgenogram. Although small lymphocyte proliferation was revealed in specimens by transbronchial lung biopsy (TBLB), immunoglobulin light chain restriction could not be seen. We attempted to verify the B-cell clonality by broncho-alveolar lavage (BAL) and a new sensitive method called kappa-lambda imaging (KLI), which was available for the detection of monoclonal B cells. Therefore, B-cell monoclonality was found. Thus, the patient was diagnosed as having primary pulmonary lymphoma (PPL). PPL may be differentiated from benign lymphoproliferative disorders such as pseudolymphoma and lymphocytic interstitial pneumonia by KLI of BAL-derived lymphocytes.

Aged↗
PubMed1993

Mesothelial splenic cyst.

A 29-year-old female was admitted because of thrombocytopenia and an abdominal mass which was palpated 5 finger breadths below the left costal margin. A computed tomographic scan of the abdomen revealed splenomegaly with a large calcified cystic lesion. The spleen was removed and the pathological examination disclosed that the cyst was monolocular and the wall was of mesothelial origin.

Adult↗
PubMed1993

A case of the human sternocleidomastoid muscle additionally innervated by the hypoglossal nerve.

An anomalous nerve supply from the hypoglossal nerve (XII) to the sternocleidomastoid muscle (SM) was observed in the right neck of an 82-year-old Japanese female. This nerve branch arose from the hypoglossal nerve at the origin of the superior root of the ansa cervicalis. The nerve fiber analysis revealed that this branch consisted of fibers from the hypoglossal nerve, the first and the second cervical nerves and had the same component as the superior root of the ansa cervicalis. SM appeared quite normal and the most part was innervated by the accessory nerve and a branch from the cervical plexus. The anomalous branch from XII supplied the small deep area near the anterior margin of the middle of the sternomastoid portion of SM. It is reasonable to think that the small deep area of SM, which was innervated by the anomalous branch from XII, occurs as the result of fusion of the muscular component from infrahyoid muscles. If the muscular component does not fuse with SM, it is thought to appear as an aberrant muscle such as the superior sternoclavicular muscle (Hyrtl) which is also supplied from a branch of the superior root of the ansa cervicalis.

Aged↗
PubMed1993

Enantiomer-enantiomer interaction of a uricosuric antihypertensive diuretic (DBCA) in renal tubular secretion and stereoselective inhibition by probenecid in the cynomolgus monkey.

1. Enantiomer-enantiomer interaction of 5-dimethylsulphamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxyl ic acid (DBCA), a uricosuric, diuretic and antihypertensive agent, was studied from the pharmacokinetics of the enantiomers following intravenous injection of individual enantiomers and racemate into male cynomolgus monkeys. Also studied was the involvement of the anion transport system in the renal excretion of DBCA by comparison of the pharmacokinetics in probenecid-treated and non-treated animals. 2. Separate administration of individual enantiomers showed higher plasma concentrations of (S)(-)-DBCA than those of the antipode, at an early period after dosing. Both enantiomers disappeared rapidly from plasma with an elimination half-life (t1/2 beta) of 0.35-0.38 h. Unbound fractions were 18.9% for the (R)(+)-enantiomer and 10.2% for the (S)(-)-enantiomer. The major portion of both enantiomers was excreted by 6 h after dosing and 77-78% of the dose was recovered within 48 h, principally as the unchanged drug. Tubular secretion contributed significantly to the renal excretion of DBCA, because tubular secretion clearance values of unbound drug (CLrf,s) were 14- to 29-fold greater than creatinine clearance. 3. The presence of the antipode decreased the tubular secretion clearance (CLrf,s) value of unbound (S)(-)-enantiomer by 30%, and tended to decrease that for the unbound (R)(+)-enantiomer, although not significantly. This indicates the occurrence of enantiomer-enantiomer interaction in the process of renal tubular secretion, and the inhibition of (S)(-)-DBCA renal excretion in the presence of the antipode. 4. Probenecid treatment significantly decreased the CLrf,s of both enantiomers, and the extent of inhibition for the (S)(-)-enantiomer (53%) was significantly higher than that for the antipode (14%). These results show that renal tubular secretion of DBCA involves an anion transport system which prefers the (S)(-)-enantiomer, and that probenecid can preferentially inhibit (S)(-)-enantiomer secretion.

Animals↗
PubMed1993

Clinical implication and prognostic significance of small lymphoma cells in the peripheral blood and bone marrow of B-cell non-Hodgkin's lymphomas.

It seems possible that small lymphoma cells (SLC) may have a role even in aggressive B-cell non-Hodgkin's lymphoma (B-NHL) such as large-cell lymphoma. However, SLC are often difficult to distinguish morphologically from normal or reactive small lymphocytes. In this study, we used a flowcytometric technique (kappa-lambda imaging; KLI) for detection of SLC. Peripheral blood (PB) and bone marrow (BM) samples taken from 41 patients with surface immunoglobulin positive (sIg+) B-NHL were analysed. SLC were detected in about 90% (37/41) of the untreated patients when either PB or BM was analysed by KLI. The presence of SLC correlated well with disease activity. However, a few SLC were present even in the PB (16%) or BM (27%) of the 31 patients who achieved complete remission, indicating that minimal residual disease (MRD) was present. In some cases, the reappearance of SLC in the PB or BM preceded clinical relapse. Furthermore, the initial volume of SLC, particularly in the BM, tended to be related to the prognosis (P = .068). These results suggest that the detection of SLC by KLI may be helpful not only for the screening and clinical staging of sIg+ B-NHL, but also for monitoring disease activity and detecting MRD. Moreover, the volume of SLC in the BM may be a useful predictor of prognosis.

Bone Marrow↗
PubMed1993

Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalospori ns with 1,2,3-triazole in C-3 side chain.

The synthesis, antibacterial activity and oral absorbability of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3 -(1H-1,2, 3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described. Their oral absorbability was influenced by the spacer length between C-3 of a cephem nucleus and C-4' of 1,2,3-triazole. The SCH2S structure was also found to contribute to their good oral absorption. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed.

Absorption↗
PubMed1993

Pharmacokinetics of intravenous ataprost alfadex, a new prostaglandin I2 analog in healthy volunteers.

Ataprost alfadex [5(E),-6,9-deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor- PGI2 alpha-cyclodextrin clathrate] is a novel PGI2 derivative. From animal studies, it is expected to be a more potent inhibitor of platelet aggregation and less hypotensive than PGI2. The pharmacokinetics of ataprost were studied in 9 healthy male volunteers during and after i.v. infusion for 2 hours at the rates of 2.5 (n = 5) and 10 ng/kg/min (n = 4). Both treatments were well tolerated by the subjects. At the end of the infusion, plasma levels of 191 +/- 76 (mean +/- SD) and 645 +/- 191 pg/ml were reached, declining rapidly with half-lives of 6.7 +/- 3.0 and 5.5 +/- 0.84 minutes at the lower and higher infusion rates, respectively. The area under the plasma concentration-time curve extrapolated to infinity increased with the dose as follows: 28.7 +/- 9.8 and 80.9 +/- 24.8 ng.min/ml. The unchanged drug was not detected in urine but a metabolite was recovered in it, reaching up to 6.0 +/- 0.85% of the total dose within the first 24 hours, the most part of which was recovered within the first 4 hours.

Adult↗
PubMed1993

[Extraction of infected pacemaker electrode using catheter and snare].

A 85-year-old man had undergone implantation of a transvenous pacemaker system in 1982. Nine years later the generator was explanted and he was underwent implantation of a new generator and electrode. After one year of the second operation, infection of the old electrode had been noted and it was not cured in spite of partial explantation of the infected electrode and appropriate antibiotic therapy. We decided to remove the infected electrode and succeeded in extraction using catheter and snare. The patient's recovery was uneventful. We suggest catheter and snare is useful for explantation of chronic transvenous pacemaker electrodes.

Aged↗
PubMed1993

[A case of bronchial lipoma treated by Nd-YAG laser surgery].

A 59-year-old man was referred to our hospital with complaint of cough. On physical examination the patient was 159 cm tall and weighted 68 kg. Chest X-ray showed an infiltrative shadow in the left lower lung field. Bronchoscopic findings revealed a polypoid tumor with smooth surface, located at the lower part of the left main bronchus and occupying over two-thirds of the left basal bronchus. A hamartoma was suspected as the result of bronchial biopsy. Endoscopic Nd-YAG laser surgery was performed. The left basal bronchus was opened. Histologically the tumor consisted mainly of mature fat tissue with collagen fibers and was diagnosed as a bronchial lipoma. Bronchial lipoma arising from the submucosal tissue of a large bronchus, occurs mainly in obese and middle-aged men. It is a rare benign tumor of the lung and only 38 cases have been reported in Japan.

Bronchial Neoplasms↗
PubMed1993

[Excellent exposure for the mitral valve by means of dissection of the interatrial groove].

A technique to approach the mitral valve through a left atrial incision under dissecting the interatrial groove is described. The dissection of the interatrial groove makes the left atrial incision more anterior and medial. Therefore excellent mitral valve exposure was obtained. 40 of 61 mitral valvular procedures during past 1.5-year period were approached through this incision. We could achieve better exposure of the mitral valve than that of conventional atrial incision technique. This technique takes not so long time and rarely carries complications including dysarrhythmia and bleeding.

Cardiac Surgical Procedures↗