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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 307 records · Page 17Linked to original sources
PubMed1995

Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.

PURPOSE: The purpose of this study was the evaluation of various factors in the formulation of guidelines for treatment of early invasive colorectal cancer, in which malignant cells extend through the muscularis mucosa into the submucosa but do not deeply invade the muscularis propria. METHOD: A total of 182 patients were followed for at least five years or until death, with early invasive cancer diagnosed between 1982 and 1989. Patients were grouped according to the level of invasion, as follows: 64 patients with slight carcinoma invasion of the muscularis mucosa (200-300 microns; sm1), 82 with intermediate invasion (sm2), and 36 with carcinoma invasion extending to the inner surface of the muscularis propria (sm3). RESULT: The configuration, diameter, and histologic grade of adenocarcinoma and lymphovascular invasion were correlated with level of invasion. After endoscopic polypectomy or local resection, 4 patients showed local recurrence and 13 patients showed lymph node metastasis. None of these 17 patients had sm1 disease. The level of invasion, configuration, and location were significant risk factors for development of lymph node metastasis or local recurrence (P < 0.05), but lymphovascular invasion, histologic grade, and diameter were not risk factors. CONCLUSIONS: Preoperative assessment of the level of invasion using this classification, in which the submucosa is divided into three depths, may decrease the incidence of unnecessary surgery for sessile polyps. Assessment according to the level of invasion is useful in the formulation of appropriate guidelines for the treatment of early invasive cancer.

Adenocarcinoma↗
PubMed1995

Inducibility of endogenous tumor necrosis factor by tumor cells from colorectal tumor patients at Dukes stage C as a novel prognostic factor following curative operation.

PURPOSE: It is well known that tumor cells secrete endogenous tumor necrosis factor (en-TNF) as a cytokine when stimulated with lipopolysaccharide (LPS). We, therefore, analyzed the biologic role of en-TNF secreted by tumor cells themselves to learn the prognosis of patients and the susceptibility of tumors to biologic response modifiers in particular. METHODS: Patients with Dukes C colorectal tumors were studied after curative operation to determine the inducibility of en-TNF by their primary cultured cells in response to LPS. RESULTS: Irrespective of the known clinicopathologic factors of the tumors, en-TNF was produced in 21 of a total of 44 patients. The group of patients with clear en-TNF production showed a significantly lower incidence of recurrence and/or metastasis and a higher survival rate than the group without en-TNF production, suggesting a strong correlation between patient prognosis and inducibility of en-TNF. CONCLUSION: Inducibility of en-TNF by tumor cells themselves can be a novel prognostic factor for patients with colorectal tumor, especially of Dukes Stage C.

Biomarkers↗
PubMed1995

Expression of the multidrug resistance-associated protein (MRP) gene in non-small-cell lung cancer.

We examined the levels of expression of the multidrug resistance-associated protein (MRP) gene quantified by Northern blot analysis in comparison with those of the MDR1 gene determined by reverse transcription-polymerase chain reaction (RT-PCR) in 104 non-small-cell lung cancer (NSCLC) specimens [59 adenocarcinoma (Ad), 40 squamous cell carcinoma (Sq), four large cell carcinoma (La) and one adeno-squamous carcinoma (AdSq)]. Thirty-three (31.7%) of the 104 NSCLC expressed the MRP gene at various levels. The NSCLC showing high (++) levels of MRP gene expression (19 out of 33, 57.6%) were predominantly squamous cell carcinomas (Ad, 5; Sq, 13; La, 1) (P < 0.05). Six of the eight NSCLCs expressing high levels of MRP mRNA and no MDR1 (MRP ++, MDR1-) were squamous cell carcinomas. Sixty-one of the 104 NSCLC patients received chemotherapy with MRP-related anti-cancer drugs [vindesine (VDS) and etoposide (VP-16)]. Twenty-three patients (37.7%) with tumour expressing high or moderate levels of MRP showed significantly worse prognoses than those with non- or low-MRP-expressing tumours (P < 0.05). These results suggest that the level of MRP gene expression is related to the histopathology and prognosis of NSCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427 in focal cerebral ischemia in rats.

The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of(+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were administered intraperitoneally immediately after ischemia and once a day for 6 successive days. FR115427 (10 mg/kg, i.p.) significantly improved neurologic deficit at 1 day after ischemia and reduced total infarct volume (54%) at 7 days after ischemia. Although FR115427 (10 mg/kg, s.c.) produced neuronal vacuolization similar to (+)MK-801, FR115427 did not produce adverse effects such as a loss of body weight, mortality, and hypothermia, in contrast to (+)MK-801. These results suggest that FR115427 may be useful in the treatment of stroke.

Animals↗
PubMed1995

Favorable course of steroid-responsive nephrotic children with mild initial attack.

The course and prognosis of idiopathic nephrotic syndrome has thus far not been found to be predicted from the severity of the manifestations at the onset. Among 66 steroid-responsive nephrotic children, eight were asymptomatic without edema and identified by chance proteinuria on a urinary screening program. The selectivity index for proteinuria (a clearance ratio of IgG to transferrin) was 0.10 or less in all of the five children examined. All of the eight children responded quickly to the prednisolone therapy. Grades of proteinuria and hypoalbuminemia were lower in the asymptomatic children than in the symptomatic children who presented with edema. Median proteinuria levels were 2.0 versus 4.2 g/day/m2 (P < 0.01), respectively, and mean serum albumin levels were 2.2 +/- 0.3 versus 1.8 +/- 0.4 g/dl (mean +/- SD; P < 0.01), respectively. None of the eight asymptomatic children relapsed for at least one year after completion of the prednisolone treatment, while, in contrast, 30 of 58 symptomatic nephrotic children relapsed during the same one-year period (P < 0.01). These findings suggest that, among steroid-responsive nephrotic children, those with mild manifestations without edema may have a milder disease and show an extremely favorable clinical course.

Child↗
PubMed1995

Suppression of cytokine production in T helper type 2 cells by nitric oxide in comparison with T helper type 1 cells.

We examined the effect of nitric oxide (NO) on cytokine production in T helper (Th) cell subsets, using murine splenic CD4+ T cells and two types of Th clones. Interferon-gamma-treated murine peritoneal exudate cells (IFN-PEC) suppressed DNA synthesis to 60% of the control level in CD4+ T cells stimulated with the anti-CD3 monoclonal antibody. The production of IL-2 and IL-4 in the CD4+ T cells decreased to 63.2% and 9.2%, respectively, of the control value by co-culture with IFN-PEC. The addition of NG-monomethyl-L-arginine (L-NMMA) partially recovered the suppression of DNA synthesis. In the presence of indomethacin, the suppression of DNA synthesis was partially inhibited and the reduction in the cytokine production caused by IFN-PEC was partially recovered. The simultaneous addition of NG-monomethyl-L-arginine (L-NMMA) and indomethacin completely inhibited not only the suppression of DNA synthesis but also the reduction in the cytokine production caused by IFN-PEC. Moreover, DNA synthesis in the Th2 clone was suppressed to a greater extent than that in the Th1 clone by co-culture with IFN-PEC. This suppression in the Th1 clone was inhibited by the addition of L-NMMA, whereas the DNA synthesis in the Th2 clone was not recovered by L-NMMA. In addition, sodium nitroprusside (SNP) suppressed IL-4 production in the Th2 clone but had no effect on IL-2 production in the Th1 clone. In the experiment of the co-culture with IFN-PEC, the inhibitory-effect of NO on T cell activation was not clarified by the influence of prostaglandins. However, in conclusion, cytokine production in Th2 cells may be more susceptible to NO than that in Th1 cells.

Animals↗
PubMed1995

Relaxant actions of isoprenaline on guinea-pig isolated tracheal smooth muscle.

1. The effects of isoprenaline on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in guinea-pig isolated tracheal muscle were studied by use of intracellular micro-electrodes and fura-2 signals respectively. Measurements of membrane potential were carried out in the presence of spontaneously-generated muscle tone, whereas fura-2 signals were measured during contraction produced by exogenous prostaglandin E2 (100 nM). The potency of isoprenaline in causing relaxation was the same in these two different situations. 2. Isoprenaline (0.01 microM) produced relaxation accompanied by 5 mV hyperpolarization. A combination of tetraethylammonium (TEA, 10 mM) and verapamil (3 microM) did not alter the effects of isoprenaline. Removal of external K+ did not increase the degree of hyperpolarization produced by isoprenaline. 3. In the presence of TEA (10 mM) and verapamil (3 microM), isoprenaline (0.03-1 microM) reduced [Ca2+]i concentration-dependently. A similar degree of inhibition was observed when isoprenaline was applied during the maintained contraction induced by prostaglandin E2 and against the contraction evoked by the addition of Ca2+ to tissues bathed in a Ca(2+)-free medium and pretreated with both isoprenaline and prostaglandin E2. 4. It is concluded that activation of TEA-sensitive Ca(2+)-dependent K+ channels does not play a significant role in isoprenaline-induced relaxation. We propose that, in the guinea-pig tracheal muscle, isoprenaline may produce relaxation mainly by inhibiting a receptor-operated pathway for Ca2+ influx across the plasma membrane which is normally activated by prostaglandins.

Adrenergic beta-Agonists↗
PubMed1995

A new genetic assay for rifampicin susceptibility of Mycobacterium tuberculosis.

A new method for testing rifampicin (RFP) susceptibility of Mycobacterium tuberculosis was developed. This method is based on detection of the internal sequence derived from 71-kDa heat shock protein mRNA in tubercle bacilli heat-treated in the presence of RFP. The target sequence was amplified by reverse transcription and PCR, followed by agarose gel electrophoretic analysis. No amplification occurred in one RFP-susceptible strain by exposure to 45 degrees C for 45 min in Middlebrook 7H9 broth containing RFP (10 micrograms/ml) after overnight incubation at 37 degrees C. On the other hand, an amplified 275-bp product was obtained from the RFP-resistant strain MY-129. In a subsequent trial using 65 clinical isolates, this method defined their RFP susceptibility levels as well as the verification of the MICs obtained by the conventional agar dilution method, with the exception of one RFP-susceptible strain. Thus, this method provides a rapid and practical system to determine RFP susceptibility in M. tuberculosis.

Antibiotics, Antitubercular↗
PubMed1995

[Epidemiological studies on enteric adenovirus gastroenteritis in children].

Enteric adenoviruses (EAd), adenovirus (Ad) types 40 and 41, have been established as causative agents of gastroenteritis. By electron microscopic (EM) survey of acute gastroenteritis in children in the Matsuyama area, Ad were detected in 275 of 6476 fecal samples obtained from 1980 to 1993. Two-hundred-thirteen Ad-positive samples were tested for serotyping by the enzyme-linked immunosorbent assay (ELISA) using three monoclonal antibodies, Ad group-specific, Ad 40 type-specific and Ad41 type-specific antibody. Of 199 samples serotyped by ELISA, 65 were identified as Ad40, 73 as Ad41, 1 as double infection with Ad40 and Ad41, and 60 as Non-EAd. About 70% of Adenovirus detected by EM were suggested to be EAd. Other epidemiological feature was as follows: EAd were detected throughout the year. The predominant serotype was Ad40 during 1980-1985, while Ad41 were observed after 1986. EAd were detected most frequently from the children aged 0-3 years. The incidence of fever in EAd positive group was lower (30%) than that (67%) in the Non-EAd positive group. The incidence of vomiting, nausea and respiratory symptoms was higher in Ad41 associated infections than Ad40.

Adenoviridae↗
PubMed1995

Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin.

The effects of single coadministrations of one of three traditional Chinese medicines, Hotyu-ekki-to, Rikkunshi-to, and Juzen-taiho-to, on the pharmacokinetics of levofloxacin (LVFX) were investigated with eight healthy volunteers in an open, random crossover fashion. Subjects each received a single oral dose of LVFX (200 mg) alone and then with a single coadministration of each Chinese medicine. There were no significant differences in any pharmacokinetic parameters of LVFX between the groups. Also, no significant changes in the urinary recovery (> 80%) and renal clearance of LVFX were observed. These results indicate that the Chinese medicines tested have no significant effect on the rate and extent of bioavailability or renal excretion of LVFX.

Adult↗
PubMed1995

Influence of a newly developed quinolone, T-3761, on pharmacokinetics of theophylline in rats.

The effect of a new quinolone, T-3761, on the pharmacokinetics and metabolism of theophylline was investigated with rats. T-3761 at a high dose (20 mg/kg of body weight) was injected intravenously 10 min before an intravenous administration of theophylline (10 mg/kg). The presence of T-3761 slightly delayed the disappearance of theophylline from plasma. Parameters related to the pharmacokinetic interaction between theophylline and T-3761 were estimated by noncompartmental methods. A significant decrease (approximately 25%) in the systemic clearance of theophylline was observed in the presence of T-3761. However, no significant changes between the control group and the T-3761-treated groups in the volume of distribution at a steady state were observed. Pretreatment with T-3761 increased the urinary excretion of unchanged theophylline (by approximately 25%) and decreased the nonrenal clearances (by approximately 30%), indicating that T-3761 inhibits the metabolism of theophylline. These findings suggest that T-3761 at the dose used in this study affects the pharmacokinetics and metabolism of theophylline.

4-Quinolones↗
PubMed1995

Role of G proteins and KCa channels in the muscarinic and beta-adrenergic regulation of airway smooth muscle.

We have examined the functional consequences of G protein coupling to calcium-activated potassium (KCa) channels using isometric tension records from guinea pig tracheal smooth muscle. After incubation with 1 microgram/ml pertussis toxin (PTX) for 6 h, the contraction response to 1 microM methacholine (MCh) was suppressed by 31.7 +/- 5.0% (n = 10). Similarly, the contraction was inhibited by 29.1 +/- 5.0% (n = 6) after application of 0.1 microM AF-DX 116, an M2-selective muscarinic receptor antagonist. Cholera toxin (CTX, 2.0 micrograms/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), also suppressed contraction by 43.9 +/- 3.3% (n = 11). The inhibitory effects of PTX, AF-DX 116, or CTX were reversed in the presence of 100 nM charybdotoxin (ChTX), a selective KCa channel inhibitor. These findings suggest that disruption of inhibitory coupling between muscarinic receptor and KCa channels mediated by PTX-sensitive G proteins, or KCa channel activation induced by Gs/adenylyl cyclase-linked processes, antagonizes muscarinic contraction. The isoproterenol concentration-inhibition curves for precontracted trachea (1 microM MCh) were shifted to the left after perfusion with PTX or AF-DX 116, and the leftward shift of the curve was blocked by ChTX. Thus direct or indirect regulation of KCa channels mediated by the inhibitory guanine nucleotide binding protein (Gi) and Gs may play a functionally important role in the mechanical antagonism by the two receptor agonists.

Adenylate Cyclase Toxin↗
PubMed1995

Effects of alkyl substituents of xanthine on phosphodiesterase isoenzymes.

The structure-activity relationships of a series of alkylxanthine derivatives were investigated. The partition coefficient of alkylxanthines enlarged with an elongation of the alkyl chain at the 1-, 3-, or 7-position of xanthine. There was a mild correlation between the apparent partition coefficient and the tracheal relaxant activity or the inhibitory activity on phosphodiesterase (PDE) IV isoenzyme, while the tracheal relaxant activity closely correlated with the PDE IV inhibitory activity. Regarding substituents at different positions, the alkylation at the 3-position increased the inhibitory activity on every PDE isoenzyme. The alkylation at the 1-position potentiated the inhibitory activity on PDE IV with the alkyl chain length, but decreased the activities on other PDE isoenzymes. The alkylation at the 7-position was characteristic in its decrease in inhibitory activity on PDE III. These results suggested that the potency of the inhibitory activity of xanthine derivatives on PDE isoenzymes is not dependent simply upon their hydrophobicity but upon change in the affinity for the active sites on PDE isoenzymes by the introduction of the alkyl group at particular positions of the xanthine skeleton.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

A xanthine derivative denbufylline inhibits negative inotropic response to verapamil in guinea pig ventricular papillary muscles, independent of its phosphodiesterase inhibitory activity.

A phosphodiesterase (PDE) III inhibitor, amrinone, inhibited both the negative inotropic actions of verapamil and nicardipine in guinea pig ventricular papillary muscle; this effect was canceled by the protein kinase A inhibitor H-89. The PDE IV inhibitor 1,3-di-n-butyl-7-(2'-oxopropyl)xanthine (denbufylline), which elicited a negative inotropic action by itself, attenuated the action of verapamil up to 10 microM, without any interaction with nicardipine. The attenuation by denbufylline was not influenced by H-89. This suggests that in the ventricular papillary muscle, denbufylline acts on some verapamil-sensitive site(s) in the membrane and interferes with the calcium channel function without involvement of its PDE inhibitory activity.

Animals↗
PubMed1995

Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart.

Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.

Adenosine↗
PubMed1995

Isolation and characterization of a hantavirus from Rattus norvegicus in a residential area of Nagoya City, Japan.

The prevalence of antibodies to hantavirus among Rattus norvegicus in Nagoya city was examined during the period from 1986 to 1993. Eight sera of 675 were antibody positive in an indirect fluorescent antibody test. Antibody positive rats were found in 1988, 1990, 1991 and 1992 and the numbers of rats were 1, 1, 3 and 3, respectively. A hantavirus strain was isolated from a rat captured in 1990 at a residential area adjoining to a pier in Nagoya port. The virus strain, named NR-9, was identified antigenically as the Seoul type of hantavirus in a neutralization test. Suckling rats inoculated with NR-9 strain survived, while those with SR-11 strain succumbed. A difference between the virulence of strains, NR-9 and SR-11 was demonstrated.

Animals↗
PubMed1995

A case of glycogen storage disease type III (glycogen debranching enzyme deficiency) with liver cirrhosis and hypertrophic cardiomyopathy.

We present a 26-year-old woman with glycogen storage disease type III (debranching enzyme deficiency) complicated with liver cirrhosis and hypertrophic cardiomyopathy. Glycogen debranching enzyme has two catalytic sites, oligo-1,4,-1,4- glucantransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33). Variability in the clinical phenotype could be a function of the involvement of one or other catalytic site, or differences in tissue expression of the defective enzyme, or both. We hypothesize that some subtypes of glycogen storage disease (GSD) type III may cause liver cirrhosis as seen in GSD type IV due to the accumulation of glycogen of abnormal structure.

Adult↗