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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 307 records · Page 17Linked to original sources
PubMed1996

Nerve growth factor (NGF) induces increase in multi-ubiquitin chains and concomitant decrease in free ubiquitin in nuclei of PC12h.

Changes in Ubiquitin-immunoreactivity after nerve growth factor (NGF) treatment were investigated in PC12h cells. Ubiquitin-immunoreactivity was increased in the nucleus of NGF-treated cells. The quantitative analysis revealed that, after 7 days of NGF treatment, almost 20% of cells had ubiquitin-immunoreactive nuclei and the frequency was increased thereafter. Levels of free ubiquitin and multi-ubiquitin chains were measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Measurements were carried out for four subcellular fractions: urea- and water-soluble extracts of nuclei and cytoplasm. Decrease in free ubiquitin was observed in water-soluble cytoplasmic extracts of NGF-treated cells, though increase in multi-ubiquitin chains in the same fraction was not observed. As for nuclei, increase in multi-ubiquitin chains and concomitant decrease in free ubiquitin were found in the water-soluble extracts after NGF treatment. Levels of multi-ubiquitin chains did not change in urea-soluble cytoplasmic extracts as well as nuclear urea-soluble ones after NGF treatment. These results indicated that multi-ubiquitination of nuclear proteins is increased during NGF-induced neuronal differentiation of PC12h cells.

Animals↗
PubMed1996

Pharmacokinetics of mycophenolate mofetil, a new immunosuppressant, in rats.

Mycophenolate mofetil (MPM), a new immunosuppressant, is the morpholinoethyl ester of mycophenolic acid (MPA). The distribution in blood and pharmacokinetics of MPA after administration of MPM were examined. The plasma to erythrocyte concentration ratio was low (0.10-0.15). MPA existed in rat plasma as the highly bound form (bound fraction was 9.79 +/- 0.57%). MPA disappeared from the systemic circulation with biexponential decay. After i.v. administration of MPM at the doses of 8.3, 16.7, and 33.3 mg/kg, the total clearance of MPA was 0.241 +/- 0.056, 0.321 +/- 0.126, and 0.317 +/- 0.092 L/h/kg, respectively. The terminal elimination half-live were 5.17 +/- 1.44, 8.89 +/- 2.76, and 7.94 +/- 2.94 h, respectively. After i.d. administration of MPM at the doses of 8.3, 16.7, 33.3, and 50.0 mg/kg, the terminal elimination half-live were 6.41 +/- 4.16, 4.49 +/- 2.20, 7.58 +/- 3.72, and 8.18 +/- 1.32 h, respectively. The mean peak times were within 30 min. The systemic availability of MPA after i.d. administration of MPM (at 8.3, 16.7, and 33.3 mg/kg) was calculated using the corresponding mean AUCiv, and the values were 84.3 +/- 35.0%, 69.9 +/- 25.7%, and 63.6 +/- 8.8%, respectively.

Animals↗
PubMed1996

Retrospective analysis of long-term surgical results in acromegaly: preoperative and postoperative factors predicting outcome.

OBJECTIVE: Sixty-one of 83 patients with acromegaly treated between 1969 and 1993 were analysed retrospectively to clarify which early postoperative factors were significant predictors of a successful long-term outcome and which preoperative factors significantly influenced the early postoperative results. PATIENTS: Of the 61 patients, 30 were operated on before 1987 and 31 afterwards. A successful long-term surgical outcome was defined as a long-term mean basal GH level < 6 mU/l (comparable to < 3 micrograms/l), a normal IGF-I level, and normal GH dynamics. RESULTS: Overall, 59% of patients (37% before 1987 and 81% after) had an early postoperative mean basal GH level < 6 mU/l, and 56% (29% before 1987 and 77% after) met all three of the specified criteria for a successful long-term surgical outcome. Statistical analysis confirmed that GH dynamics and postoperative mean basal GH level < 6 mU/l were significant predictors of the long-term surgical outcome, whereas the postoperative IGF-I level alone was not. On the other hand, abnormal preoperative GH dynamics were normalized in all patients with a postoperative mean basal level < 6 mU/l. In addition, there were no patients showing an unsuccessful long-term outcome in those associated with both the early postoperative mean basal GH level < 6 mU/l and normalization of the IGF-I level. Therefore, measurement of the early postoperative mean basal GH level and the IGF-I level may be an economical and simple guide to predict the long-term surgical outcome. Moreover, multivariate analysis indicated that cavernous sinus invasion was an independent significant factor influencing the early postoperative outcome. CONCLUSIONS: Successful long-term surgical outcome may be predicted if early postoperative mean basal GH level is reduced to < 6 mU/l (< 3 micrograms/l) and IGF-I level becomes normal. This study also confirms that early diagnosis and treatment by an experienced endocrinologist and neurosurgeon can improve the operative results in patients with acromegaly.

Acromegaly↗
PubMed1996

Expression of type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in newly established human oral malignant tumor lines.

We have established 11 human oral tumor lines maintained as in subcutaneous xenografts in BALB/c athymic nude mice, and examined their metastatic and invasive characteristics, and expression of type IV collagen-degrading metalloproteinases and their intrinsic inhibitors (TIMPs). These tumor lines have approximately maintained the histological appearance of the parental tumors. Generally, human tumors maintained subcutaneously in nude mice metastasize only very rarely. However, one mesenchymal tumor line, a malignant melanoma designated MTN, was found to metastasize spontaneously to the lung and a lysate of the MTN cells had a high level of type IV collagenolytic activity. Among epithelial tumor lines, SKH, derived from squamous cell carcinoma, showed high expression of TIMP-1 in Northern blotting and had low type IV collagenolytic activity. SN, derived from squamous cell carcinoma, also showed low type IV collagenolytic activity. These two squamous cell carcinoma lines showed a non-invasive growth pattern when they were implanted orthotopically into the tongues of athymic nude mice. By contrast, tumor lines which showed higher type IV collagenolytic activity had a tendency to grow invasively in mouse tongue. These findings suggest that our 11 newly established tumor lines may provide useful systems for studies of tumor biology and therapy.

Adenocarcinoma↗
PubMed1996

Antiarrhythmic action of rilmenidine on adrenaline-induced arrhythmia via central imidazoline receptors in halothane-anaesthetized dogs.

1. To elucidate the role of central imidazoline receptors in the genesis of adrenaline-induced arrhythmias under halothane anaesthesia, we investigated the effects of rilmenidine, a selective agonist at imidazoline receptors, on this type of arrhythmia in dogs. Rilmenidine (1, 3, 10 micrograms kg-1, i.v.) did not affect basal haemodynamic parameters (heart rate and blood pressure), but dose-dependently inhibited adrenaline-induced arrhythmias under halothane anaesthesia. 2. Although, rilmenidine has a weak affinity for alpha(2)-adrenoceptors, pretreatment with idazoxan (10 micrograms kg-1, intracisternally i.c.), an imidazoline receptor antagonist which has also alpha(2)-adrenoceptor blocking potency, blocked the antiarrhythmic effect of rilmenidine (10 micrograms kg-1, i.v.). In contrast, pretreatment with rauwolscine (20 micrograms kg-1, i.c.), a classical alpha(2)-adrenoceptor antagonist with little affinity for imidazoline receptors, did not affect the effect of rilmenidine (10 micrograms kg-1, i.v.). Furthermore, bilateral vagotomy completely blocked the antiarrhythmic action of rilmenidine (10 micrograms kg-1, i.v.). 3. It is suggested that the antiarrhythmic action of rilmenidine is due to the activation of central imidazoline receptors and that vagal tone is critical for this action of rilmenidine.

Adrenergic alpha-Agonists↗
PubMed1996

Effects of murine lysozyme on lipopolysaccharide-induced biological activities.

We have demonstrated that egg-white lysozyme (EW-LZM) bound to lipopolysaccharide (LPS), reduced the lethal toxicity and the biological activity of LPS. In this study, the interaction of LPS with murine lysozyme (M-LZM) and the modulation of biological activities were investigated. M-LZM was prepared from the culture supernatant of the murine macrophage cell line RAW264.7 by ion-exchange and gel filtration chromatographies and dialysis. Two types of M-LZM, murine M lysozyme (MM-LZM) and murine P lysozyme (MP-LZM), were purified from the supernatant. The enzymatic activities of both MM-LZM and MP-LZM were inhibited by LPS and their effects were affected by the temperature and the ionic strength. TNF-alpha production from RAW264.7 by LPS was inhibited by mixing with MM-LZM and MP-LZM. MP-LZM inhibited TNF-alpha production stronger than MM-LZM. Considering these facts, we suggested that M-LZM, like EW-LZM, make a complex with LPS to reduce the toxicity of LPS together with inhibiting the enzymatic activity.

Amino Acid Sequence↗
PubMed1996

Oral sustained-release cisplatin capsule.

An oral sustained-release cisplatin preparation was prepared by combining microporous water-insoluble pharmaceutical polymer, ethylcellulose, a membrane and a gel-forming polymer, poly(acrylic) acid (Carbopol). As cisplatin is an extremely hydrophilic and small compound, it was difficult to control the release rate solely by the micropores on the ethylcellulose capsule. To retain cisplatin within the capsule, gel-forming polymer was formulated inside the capsule. The release rate of cisplatin was dependent both on the number of micropores of the capsule and the formulated amount of Carbopol. The number of micropores ranged from 20 and 30 to 60, and the formulated amount of Carbopol varied from 15 to 100 mg. In-vitro release experiments suggested that the release rate decreased as the formulated amount of Carbopol increased when the pore number was 60 and 30. However, when pore number was decreased to 20, the effect of the amount of Carbopol was not clearly observed. In the in-vivo study using rabbits, the sustained-release cisplatin capsule was evaluated in comparison with solution after oral administration of 20 mg drug. With the pore number of 60, Cmax was 0.46 +/- 0.02 microgram mL-1 at 4 h and thereafter serum concentrations declined rapidly. When the pore number was 30, serum cisplatin level-time profiles showed long-acting patterns and AUC was reversely correlated with the formulated amount of Carbopol. Cmax and tmax were 0.41 +/- 0.02 microgram mL-1 and 3.33 +/- 0.88 h, respectively and 0.23 +/- 0.01 microgram mL-1 was obtained at 24 h after oral administration of capsule having 30 pores and 15 mg of Carbopol. We conclude that the possibility of developing an oral sustained-release cisplatin preparation is feasible.

Acrylic Resins↗
PubMed1996

Clonal propagation of Epstein-Barr virus (EBV) recombinants in EBV-negative Akata cells.

We lack a host cell supporting an efficient lytic replication of Epstein-Barr virus (EBV). Recently, we isolated EBV-negative cell clones from the Akata cell line (referred as Akata- [N. Shimizu, A. Tanabe-Tochikura, Y. Kuroiwa, and K. Takada, J. Virol. 68:6069-6073, 1994). Since the parental Akata line is one of the highest EBV producers, we examined whether Akata- cells had become a good host for EBV propagation. The parental Akata cells have about 20 copies of EBV plasmid per cell. A drug resistance gene was inserted into one of them by homologous recombination. The resultant virus preparation, a mixture of wild-type and recombinant EBV, was used to infect Akata- cells. After incubation in the selective medium, drug-resistant Akata- cell clones were isolated and proved to be infected with recombinant EBV only. By treatment of the cells with antiimmunoglobulin antibodies, a large amount of recombinant EBV (i.e., more than 10 microg/1-liter culture) was produced. In contrast, three other B-lymphoma lines, BJAB, Ramos, and Louckes, were nonpermissive for virus replication. These results indicate that Akata- cells are suitable for propagation of recombinant EBV clonally, which becomes a powerful tool for determining EBV genetics and which makes it possible to use EBV as a vector for gene therapy.

B-Lymphocytes↗
PubMed1996

Tongue, jaw, and lip muscle activity and jaw movement during experimental chewing efforts in man.

The electromyographic (EMG) activity of the human genioglossus (GG) muscle during chewing efforts is not fully understood. In this study, the EMG activity of the human GG muscle during unilateral gum chewing was illustrated and correlated with the activities in the anterior temporalis (AT), the anterior digastric (DG), and the inferior orbicularis oris (OI) muscles. GG muscle activity was measured with customized surface electrodes, while other muscles were recorded with conventional surface electrodes. EMG activities during tongue displacement and the articulation of long vowels, recorded by the customized electrodes, were consistent with the recordings obtained by fine wire electrodes placed in the GG muscle. Jaw displacement was monitored by means of a kinesiograph with a transducer attached to the mandibular central incisors. Mean normalized GG muscle activity showed an onset in the last one-fifth of the intercuspal phase, gradually increasing during jaw-opening, and at its greatest immediately before the maximum jaw-opening position. It then decreased during jaw-closing and ceased in intercuspation but showed a small rebound in the third fifth of the intercuspal phase. The GG muscle burst showed phase lags with the DG and OI muscles and an opposite phase with the AT muscle (all P < 0.0001). All correlations were statistically significant (all P < 0.0001, r values between 0.88 and 0.97). The results suggest central coordination of the timing of the activities of the jaw, lip, and tongue muscles in chewing.

Adolescent↗
PubMed1996

Tongue volume in human female adults with mandibular prognathism.

It has often been hypothesized that a large tongue leads to an enlargement of the mandible and therefore contributes to the development of mandibular prognathism. We examined (1) whether the tongue volume in human subjects with mandibular prognathism was larger than that in subjects with good occlusion and (2) whether the tongue volume and the pharyngeal capacity correlated with the morphological characteristics of dento-skeletal structures. Magnetic resonance images of the tongue and its surrounding structures were recorded for female adult volunteers with good occlusion (control group, n = 10) and patients with mandibular prognathism (test group, n = 16). Lateral cephalograms were obtained for the patients. No significant differences were determined for the tongue volume or the pharyngeal capacity between the two groups. The tongue volume did not correlate with the pharyngeal capacity (r = 0.280, p = 0.166). The tongue volume correlated with the facial angle (r = 0.548, p = 0.028), the Y-axis (r = 0.539, p = 0.031), and the angle nasion-A point-pogonion (r = 0.540, p = 0.031). These results suggest that the tongue volume is accounted for by the combined horizontal and vertical location of the chin and symphysis, but do not support the conventional clinical surmise that large tongue volume is inherent in patients with mandibular prognathism.

Adult↗
PubMed1996

Thiopalmitic acid-mediated Fe(III)-nitrilotriacetate reduction and lipid peroxidation.

The mechanism of the antioxidant action of thiopalmitic acid (SH-Pal) was examined in an in vitro system measuring ferric (Fe(III)-nitrilotriacetate (NTA)- and Fe(III)-NTA/ascorbic acid (AsA)-induced lipid peroxidation of rat liver phospholipid liposomes and microsomes. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances (TBARS). SH-Pal and glutathione (GSH) scarcely stimulated the Fe(III)-NTA-induced lipid peroxidation in contrast with the mode of action, being similar to those produced by reducing-agent antioxidants such as cysteine and AsA. SH-Pal reduced iron similar to the action produced by AsA and cysteine, but not that of GSH under the same conditions. Also, the reduction of iron by SH-Pal did not exhibit a pH dependency. Similarly, microsomal lipid peroxidation and oxygen consumption induced by Fe(III)-NTA/AsA were inhibited by the addition of SH-Pal in a time and dose dependent fashion, but GSH and cysteine exhibited a lower protective action. Time course studies on TBARS formation and oxygen consumption indicated the ability of SH-Pal to inhibit initiation and propagation reactions. Moreover, the microsomal lipid peroxidation induced by Cumene hydroperoxide (CumOOH) was progressively suppressed by the addition of increasing amounts of SH-Pal. These findings suggest that the antioxidant action of SH-Pal is partly due to complete reduction of iron at a faster rate and inhibition of oxygen consumption during the progress of the peroxidation. Further, SH-Pal has a protective action against free radical damage by hydroperoxy radical.

Animals↗
PubMed1996

Effects of methyl 9(or 10)-hydroxy-10(or 9)-mercaptostearate and hexadecanethioic S-acid on cupric ion- or 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidation of low density lipoprotein.

The preventive effects of two antioxidants, methyl 9(or 10)-hydroxy-10 (or 9)-mercaptostearate (SH-S) and hexadecanethioic S-acid (thiopalmitic acid, SH-Pal) against the oxidative modification of low density lipoproteins (LDL) induced by cupric ion or a water soluble initiator of peroxyl radicals, 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), were studied by measuring thiobarbituric acid-reactive substances (TBARS). SH-S acted as an effective antioxidant in the oxidative modification of LDL induced by either cupric ion or AAPH. Interestingly, SH-S completely inhibited the formation of fluorescence products and decreased both the fluorescence and alpha-tocopherol content in LDL induced by cupric ion, and reduced 1,1-diphenyl 2-picrylhydrazyl (DPPH) used as a stable free radical model. The antioxidative effect was effectively prevented by the addition of increasing amounts of N-ethylmalemide (NEM) to the system. SH-Pal also inhibited the cupric ion-induced LDL oxidation, but showed little inhibitory effect on the AAPH-induced LDL oxidation. Moreover, SH-Pal was reduced to palmitic acid during the AAPH-induced LDL oxidation. These findings indicate that SH-S protects against oxidative damage of LDL in vitro, and that it acts as a free radical in peroxidation. In addition, this study shows that SH-Pal doesn't act as an efficient antioxidant in AAPH-induced lipid peroxidation.

Amidines↗
PubMed1996

Coronary artery to pulmonary artery fistula with two giant saccular aneurysms in an elderly patient determined noninvasively.

An 87-year-old woman was admitted to our hospital on an emergency basis with atypical chest pain and dyspnea. She had a continuous precordial murmur. Electrocardiogram showed no evidence of myocardial ischemia, but chest X-ray showed marked enlargement of the cardiac silhouette and an abnormal calcified vascular structure. Computed tomography of the chest revealed large abnormal masses next to the heart. Two-dimensional echocardiography showed enlargement of the main trunk of the left coronary artery and 2 giant saccular aneurysms. Abnormal diastolic inflow to the main pulmonary trunk was also observed by color flow imaging. These findings were supported by data obtained using magnetic resonance imaging and transesophageal echocardiography. Based on the above findings, we diagnosed this case as a coronary artery fistula originating from the proximal left anterior descending artery associated with 2 giant saccular aneurysms draining into the pulmonary artery. To our knowledge, this is the oldest patient ever reported with such an anomaly. This case emphasizes that a good prognosis is possible even with a very pronounced visible structural abnormality.

Aged↗
PubMed1996

A study of anterior pituitary hormones secretion in patients with glioma receiving interferon-beta treatment.

Human interferon beta (IFN-beta) has been used for the treatment of patients with benign and malignant astrocytomas. The effect of IFN-beta on pituitary function, however, has not been precisely evaluated before. In this study the serum levels of various anterior pituitary hormones including GH, PRL, ACTH, and TSH were measured to determine the effects of IFN-beta on pituitary endocrine function in 19 consecutive glioma patients receiving IFN-beta. Daily doses of 3 x 10(6) U of IFN-beta were administered as a 30-min intravenous drip infusion beginning at 0800 h every morning during the first week and then 4 times a week for additional 6 weeks. Blood samples were taken on the day prior to administration as controls (0900 h and 1500 h), and on the first day of administration (0900 h and 1500 h) and after 7 days of administration (0900 h) in order to determine the acute and chronic or integrated effects of IFN-beta on the above pituitary hormones. No significant change in serum concentrations of any of the pituitary hormones examined was observed, suggesting that human natural IFN-beta used for the treatment of gliomas has no significant effect on the secretion of these hormones from the pituitary in these patients.

Adolescent↗
PubMed1996

Lack of CD54 expression and mutation of p53 gene relate to the prognosis of childhood Burkitt's lymphoma.

Expression of the intercellular adhesion molecule-1 (CD54) as well as the mutations of p53 gene were studied in childhood Burkitt's lymphoma (BL). Expression of CD54 was identified in 6 of 15 fresh BL cases. Mutations of p53 gene, analyzed by polymerase chain reaction-single stranded chain polymorphism followed by sequencing, were found in 5 of 14 cases examined. Interestingly, all the cases with p53 mutation were CD54 negative. This high frequency of p53 mutation in the CD54 negative group prompted us to analyze the clinical features of these cases. Six of 15 cases died within 21 months after initiation of therapy and five of these were CD54 negative. In addition, four of these had p53 mutation. These results suggest that the lack of CD54 by BL cells may provide the background for the mutation of p53 gene to occur which could result in the transformation to a more aggressive phenotype.

Adolescent↗
PubMed1996

Effect of food intake on the delivery of fluorescein as a model drug in colon delivery capsule after oral administration to beagle dogs.

The effect of food on the release time of a model drug, fluorescein (FL), has been studied after oral administration to beagle dogs in colon delivery capsule in comparison to conventional gelatin capsule and enteric capsules. The dose of FL was 30 mg for each animal. After oral administration of each test preparation in fasted or postprandial condition (100 grams of commercial solid food was given at 30 min before drug administration), blood samples were collected and plasma FL concentrations were measured spectrofluorometrically. Pharmacokinetic analysis was performed with plasma FL concentration vs. time data and the following parameters were determined; Tmax (the time when plasma FL concentration reaches to its maximum concentration), Cmax (peak plasma FL concentration), Tlag (the time when FL appeared at first into the systemic circulation), AUC (area under the plasma FL concentration vs. Time curve) and MRT (mean residence time). For gelatin capsule, mean Tmax appeared at 0.83 +/- 0.33 (S.E.) h after administration and MRT was 2.67 +/- 0.21 h in fasted condition. By feeding, Tmax and MRT increased to 1.50 +/- 0.76 h and 3.09 +/- 0.49 h. For two enteric HPMCP and Eudragit S capsules, MRT were 2.90 +/- 0.48 h and 5.24 +/- 0.32 h in fasted condition, and 11.30 +/- 1.10 h and 12.83 +/- 0.34 h in postprandial condition, respectively. Tlag also increased by postprandial administration. As colon delivery capsule, time-controlled release capsule (TCC) and two types of intestinal inner pressure-controlled release capsules (PCC) (#1 is a separate type and #2 is a seamless one) were tested. MRT of TCC was 4.76 +/- 0.29 h and 6.43 +/- 0.66 h in fasted and postprandial conditions, respectively. This capsule did not receive the effect of food intake. For #1 PCC, MRTs were 5.32 +/- 0.22 h and 12.28 +/- 0.26 h in fasted and postprandial conditions, respectively. For #2 PCC, MRTs were 5.51 +/- 0.26 h and 13.36 +/- 0.84 h in fasted and postprandial conditions, respectively. In addition, the effect of two times feedings was studied with two PCCs and longer MRTs, 28.44 +/- 1.39 h and 26.32 +/- 1.64 h, were obtained. The release time of FL from PCCs increased by postprandial administration. As compared to the results on two enteric capsules, these PCCs are thought to disintegrate in the colon. However, TCC is thought to disintegrate in the stomach after postprandial administration.

Administration, Oral↗
PubMed1996

[Expression of CD44 variant 6 and its metastatic potential in squamous cell carcinoma of the oral cavity].

Using antihuman CD44 variant 6 monoclonal antibody (2F10), immunohistochemical screenings were performed for 38 oral squamous cell carcinoma cases and 10 oral mucosa in healthy cases as normal counterpart. Normal epithelium in the oral surface was stained intensely by the antibody. The reactivity was particularly strong in the spinous layers of stratified squamous epithelium. Cells in the basal layers exhibited moderate staining. In contrast, expression of CD44v6 tended to be downregulated in 38 oral squamous cell carcinoma materials. Interestingly, more faint or no staining by the anti-CD44v6 monoclonal antibody was found in the primary squamous cell carcinomas involving regional lymphnode metastasis. Downregulation of CD44v6 isoform was suggested to occur during regional lymphnode metastasis on oral squamous, cell carcinomas.

Carcinoma, Squamous Cell↗