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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 271 records · Page 15Linked to original sources

The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1.

In the present study, we investigated the interactions between antibiotics, especially beta-lactam antibiotics, and rat renal organic anion transporter 1 (OAT1). [(14)C]p-Aminohippurate (PAH) uptake via OAT1 expressed in Xenopus laevis oocytes was inhibited by all of the penicillins and cephalosporins tested. Penicillin G, carbenicillin, cephaloridine, cephalothin, cefazolin, and cephalexin inhibited [(14)C]PAH uptake via OAT1 in a competitive manner (K(i) = 0.29-2.33 mM). Cinoxacin, a quinolone gyrase inhibitor, also inhibited PAH uptake via OAT1. Other antibiotics, such as gentamicin, streptomycin, and vancomycin, which do not contain anionic moieties, did not interact with OAT1. [(3)H]Penicillin G and [(14)C]cephaloridine were demonstrated to be transported via OAT1. Using the cells that stably expressed OAT1, we analyzed the cytotoxicity of several beta-lactam antibiotics. Cells expressing OAT1 showed higher susceptibility to cephaloridine (a potentially nephrotoxic beta-lactam antibiotic) toxicity than did control cells. The present study suggests that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of beta-lactam antibiotics. Furthermore, the culture cell system expressing OAT1 was revealed to be useful for the prediction of the nephrotoxicity of beta-lactam antibiotics.

Animals↗

[Knobby-like choroidal neovascularization accompanied with retinal pigment epithelial detachment].

PURPOSE: To evaluate the clinical features of knobby choroidal neovascularization (CNV) which was detected using indocyanine green (ICG) angiography and the association between knobby CNV and idiopathic polypoidal choroidal vasculopathy (IPCV). METHOD: We studied 164 eyes with retinal pigment epithelial detachment (PED) accompanied with CNV. These patients were older than 50 years. We detected knobby CNV in 96 eyes of 164 PED eyes (58.5%). Knobby CNV was defined as follows: knobbed blood vessels were observed from the early phase and remained hyperfluorescent through the ICG angiography. We classified 3 groups on the basis of the types of vessels with knobby CNV: group I, multiple isolated knobby CNVs without continuous vessels (24 eyes); group II, knobby dilatations in some parts of CNV (45 eyes); group III, network vessels ending in multiple aneurysmal swelling as in IPCV (27 eyes). RESULT: We found knobby CNV in only 20% of eyes with serous PED, but about 70% in neovascular, serosanguineous, and hemorrhagic PED. The ratio of each group showed no distinction statistically. Knobby CNV mostly appeared in macular areas, and was frequently accompanied with subretinal or subpigment epithelial hemorrhage. Subretinal reddishorange lesions were seen in 50% of group I, 60% of group II, and 89% of group III. Knobby CNV showed occult CNV in fluorescein angiography. In late phase ICG angiography, knobby CNV leaked ICG. New lesions occurred in all groups. CONCLUSION: We think that knobby CNV is a common finding in subpigment epithelial neovascularization, and that IPCV vascular lesion is one type of subpigment epithelial neovascularization.

Aged↗

Effects of potassium channel blockers on CO2-induced slowly adapting pulmonary stretch receptor inhibition.

In anesthetized, artificially ventilated rabbits with vagus nerve section, inhalation of CO(2) gas mixtures (tracheal CO(2) concentration ranging from 8.0 to 10.2%) for 60 s decreased slowly adapting pulmonary stretch receptor (SAR) activity during both inflation and deflation. The magnitude of decreased receptor activity during deflation had a more pronounced effect than that seen during inflation. CO(2) inhalation did not cause any significant change in tracheal pressure (P(T)) as an index of bronchomotor tone. Intravenous administration of 4-aminopyridine (0. 7 and 2.0 mg/kg i.v.), a K(+) channel blocker, which dose-dependently increased SAR activity during deflation and had no effect on P(T), abolished or attenuated the decrease in SAR activities induced by CO(2) inhalation in a dose-dependent manner. The K(+) channel blocker tetraethylammonium (2.0 and 6.0 mg/kg i.v.) that did not significantly alter either basal SAR discharge or P(T) had no effect on the inhibitory responses of receptor activity to CO(2) inhalation. These results suggest that the inhibitory mechanism of CO(2) inhalation on SARs may be involved in the activation of 4-aminopyridine-sensitive K(+) channels in the nerve terminals of SARs.

4-Aminopyridine↗

Renal cell carcinoma in children: experience at a single institution in Japan.

PURPOSE: We analyzed the presentation, treatment and survival of 4 children with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the pathological and hospital records of 4 Japanese children diagnosed with renal cell carcinoma at our hospital from 1970 to 1998. RESULTS: In the 1 boy and 3 girls with an average age of 8 years 7 months at diagnosis the most common presenting complaints were gross hematuria in 75% and a palpable abdominal mass in 50%. Computerized tomography revealed characteristic calcification within the tumor in 3 of the 4 patients (75%). In the remaining case the lesion had high density areas with microcalcification, as confirmed by histopathological study. In 2 patients with regional lymph node metastasis calcification was also observed in the metastatic lesions. Disease was stages I to III in 1, 1 and 2 patients, respectively. All patients underwent transabdominal nephrectomy with regional lymphadenectomy. One patient with stage I disease had multiple metastases 15 months later and died of disease 55 months postoperatively. However, the remaining 3 patients received adjuvant interferon therapy and they are without evidence of recurrence a mean of 51.3 months postoperatively. CONCLUSIONS: Calcification within the tumor and/or metastatic lesions or high density areas in the tumor on screening computerized tomography are characteristic findings suggestive of pediatric renal cell carcinoma. Adjuvant therapy with interferon may provide some benefit in select pediatric patients. Further studies of a larger number of pediatric renal cell carcinoma cases may be necessary to establish the optimal diagnostic and therapeutic regimen.

Carcinoma, Renal Cell↗

[Persistent primitive olfactory artery: report of 5 cases].

Five cases of a persistent primitive olfactory artery are reported. The anomalous artery coursed anteromedially along the ipsilateral olfactory nerve and made a hairpin turn, supplying the circulation of the anterior cerebral artery. It was proposed that a primitive embryonic olfactory artery had remained as this artery. A cerebral aneurysm was located at the hairpin curve of the artery. Hemodynamic stress is considered to have an important role in aneurysm formation. Any aneurysm occurring at an artery should be considered for surgical treatment.

Aged↗

Perception and conception: separate memory systems in the medial temporal lobe.

The purpose of the present study was to investigate, by using positron emission tomography, whether the functionally different types of information are subserved by different memory systems in human medial temporal lobe structures. Before explicit retrieval tests during scans, subjects studied words in perceptually and conceptually processed manners separately. It was found that different parts of the medial temporal lobe structures were involved in each of the different conditions. These results indicated that perceptually and conceptually processed types of information were subserved by at least two partially segregated memory systems in human medial temporal lobe structures.

Adult↗

[Estimation of 99mTc-GSA receptor amount by non-linear 3-compartment model: ligand-receptor binding model without blood sampling].

99mTc-GSA (galactosyl serum albumin) receptor amount (Ro) was estimated by a non-linear 3-compartment model of the ligand-receptor binding without blood sampling. Forward/reverse rate constants and receptor amount were assumed to be variable. Relationship between this parameter and other conventional parameters including ICG R15 (15-minutes retention rate of indocyanine green) was evaluated for 43 surgical candidates with liver tumors. Linear relationships between Ro and HH15 and LHL15 were R2 = 0.73 and 0.72, respectively. Linear relationship between Ro and Rmax, the maximum removal rate, is also good (R2 = 0.84), and the regression line (y = 0.038x + 0.066) was slightly over 0 at y-interception. Linear relationship between Ro and ICG R15, was poor (R2 = 0.39) and relationship was rather a concave shape. Linear relationship of reduction rate between Ro and non-tumor tissue volume of the liver, which assessed at the same day of two weeks after the operation, was y = 1.09x - 0.01 (R2 = 0.82). GSA receptor amount, Ro, seems to change proportional to non-tumor liver tissue volume changing before and after hepatectomy. Complementary to ICG R15, it may be an useful and intuitive parameter for hepatectomy.

Asialoglycoprotein Receptor↗

[Minimally invasive surgery for single valvular heart disease].

Two patients underwent valve surgery using the minimally invasive approach. A 51-year-old man underwent mitral valve repair for chronic mitral regurgitation due to prolapse of the posterior mitral leaflet. The left-half of his sternum was cut in "C" shape below the level of the second intercostal space, and all of the arterial or venous cannulas were inserted via this single access. A 37-year-old man underwent aortic valve replacement for aortic valve regurgitation due to infective endocarditis. Right upper partial sternotomy between the first and fourth intercostal space was selected for this aortic valve surgery. The median skin incisions were as small as 12 and 9 cm. Postoperative recovery was very smooth. Minimally invasive approach using selected partial sternotomy provides acceptable results with a good exposure, and is an alternative approach to valve surgery.

Adult↗

[Comparison of the newly developed MB redox system with mycobacteria growth indicator tube (MGIT) and 2% Ogawa egg media for recovery of mycobacteria in clinical specimens].

The rate of recovery and the mean time to detection of mycobacteria in clinical specimens were determined in a newly-developed MB Redox system based on liquid medium, and the results were compared with those of MGIT and 2% Ogawa egg media. From 587 sputum specimens processed, totally 203 mycobacterial isolates were detected, of which 177 (87.2%) with MB Redox, 185 (91.1%) with MGIT and 133 (65.6%) with 2% Ogawa medium. The difference in the percentages of positive cultures between either of the two liquid media and 2% Ogawa medium was significant (p < 0.0001). The mean time to detection of the Mycobacterium tuberculosis complex was 17.5 days with MB Redox, 18.7 days with MGIT, and 26.2 days with 2% Ogawa medium. The contamination rates were 1.5, 1.7, and 4.1% for MB Redox, MGIT, and 2% Ogawa medium, respectively. In conclusion, both MB Redox and MGIT systems, based on liquid medium, are more efficient than 2% Ogawa medium for the recovery of mycobacteria in clinical specimens.

Bacteriological Techniques↗

Estimation of functional liver reserve in patients before cardiac surgery using antipyrine plasma clearance test.

BACKGROUND: Hyperbilirubinemia is not uncommon and is sometimes fatal after valvular surgery. One important cause of it is a poor functional liver reserve, however, conventional tests reflect hepatic blood flow and do not offer precise evaluation of the pure functional liver reserve. Antipyrine has particular pharmacological properties, and its plasma clearance represents quantitatively the functional capacity of the liver. In this study, we measured antipyrine plasma clearance in cardiac surgical patients and evaluated the feasibility of using this parameter as a predictor of the risk of postoperative hyperbilirubinemia. METHODS: The plasma clearance of antipyrine was measured preoperatively in 40 cardiac patients undergoing mitral and/or tricuspid valvular surgery and its relations with hemodynamics or postoperative course were studied. RESULTS: Antipyrine clearance in preoperative patients was 0.365+/-0.175 (mean +/- SD) ml/min/kg, lower than the normal range (0.405+/-0.04 ml/min/kg), and showed no correlation with cardiac index, while the plasma disappearance rate of indocyanine green depended on the cardiac index. The maximum postoperative total bilirubin level showed significant correlation with antipyrine clearance (r=-0.699); this correlation coefficient was greater than that with indocyanine green (-0.477). The correlation was more prominent in patients with cardiac dysfunction. Furthermore, antipyrine clearance showed significant predictability of the duration of ICU stay. CONCLUSIONS: Antipyrine clearance provides a precise estimate of functional liver reserve which is independent of hemodynamics and predicts the risk of postoperative hyperbilirubinemia in preoperative cardiac patients.

Adult↗

A System to Find Genetic Networks Using Weighted Network Model.

We are developing a system which finds a genetic network from data obtained by multiple gene disruptions and overexpressions. We deal with a genetic network as a weighted graph, where each weight represents the strength of activation from a gene to another gene. In this paper, we explain the overview of our system, and our strategy to visualize the weighted network. We also study the computational complexity related to the visualization.

Journal Article↗

Layer-specific NO dependence of long-term potentiation and biased NO release in layer V in the rat auditory cortex.

1. We investigated the role of nitric oxide (NO) in the induction of long-term potentiation (LTP) in slices prepared from the rat auditory cortex. 2. Tetanic stimulation of layer IV elicited LTP of field potentials in layer II-III (LTPII-III) and in layer V (LTPV). The magnitude of LTPII-III measured at 30 min after tetanic stimulation was 171 +/- 9% (n = 15, mean +/- s.e.m.) of the control measured before tetanic stimulation, while that of LTPV was 138 +/- 3% (n = 17). 3. NO synthase (NOS) inhibitors had no apparent effect on LTPII-III, but LTPV was significantly suppressed (P < 0.001). This suppression of LTPV was significantly antagonized by a NO donor (P < 0.001) or a cGMP analogue (P < 0.001). 4. Small non-pyramidal neurones in the auditory cortex were stained with an anti-neuronal NOS antibody. More neurones were stained with the antibody in the deeper cortical layers. 5. We measured neocortical NO release with electrochemical NO probes. Layer IV stimulation elicited significantly more NO release in layer V than in layer II-III (P < 0.001). The amplitude of the increase in NO concentration elicited by stimulation at 20 Hz for 5 s was 380 +/- 14 pM (n = 55) in layer V and 55 +/- 8 pM (n = 5) in layer II-III. 6. NO release in layer V was partially but significantly suppressed by non-NMDA (P < 0.002) or NMDA (P < 0.002) receptor antagonists. Simultaneous application of the antagonists of the two types blocked NO release almost completely. 7. These results clearly indicate the NO dependence of the induction of LTPV, and the greater NO release in the deeper layer of the rat auditory cortex.

Animals↗

Role of basic fibroblast growth factor in the pathogenesis of moyamoya disease.

The pathogenesis of moyamoya disease is still under investigation. In this study, the authors focus on the role of cytokines in the pathogenesis of moyamoya disease by using immunohistochemical analyses. The authors examined two specimens in the circle of Willis obtained at autopsy from two patients with moyamoya disease and two additional specimens obtained from control cadavers with atherosclerotic stenosis of the intracranial carotid arteries. Immunohistochemical examinations of the sections of the major intracranial arteries were performed using antismooth muscle cells (SMCs), monocytes, growth factor, cell nuclear antigen, and fragmented DNA antibodies. Basic fibroblast growth factor (bFGF) staining was present only in the endothelial cells of the moyamoya disease specimens and was not seen in control samples. In addition, the endothelial cells and SMCs in the media were positive for terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick-end labeling of fragmented DNA method but not in the SMCs in the intima in moyamoya disease specimens, which indicates that an apoptotic process is active in only SMCs in the media but not in the intima. In conclusion, it is suggseted that the presence of bFGF in the media specifically seen in moyamoya disease suppresses the apoptotic process of SMCs in the intima.

Journal Article↗

Ceramide inhibits inwardly rectifying K+ currents via a Ras- and Raf-1-dependent pathway in cultured oligodendrocytes.

Ceramide is a lipid mediator implicated in apoptosis induced by proinflammatory cytokines in many cell types, including oligodendrocytes (OLGs). To determine whether ceramide modulates transmembrane signaling events in OLGs, we studied its effect on intracellular Ca2+ (Cai), resting membrane potential and inwardly rectifying K+ currents (IKir) in cultured neonatal rat OLGs. We report here that (1) exposure to C2-ceramide (cer) rarely increases OLG Cai, whereas sphingosine elicits sustained increase in Cai; (2) cer causes OLG depolarization, an effect mimicked by sphingosine-1-phosphate but not by sphingosine; and (3) cer, but not its inactive analog dihydroceramide, inhibits OLG IKir. The cer effect is attenuated by Ras antibody Y13-259, by protein kinase C inhibitory peptide (19-36), and by suppression of c-Raf-1 expression with antisense raf-1 oligonucleotides. We conclude that cer-induced OLG depolarization is mediated via inhibition of IKir by a Ras- and raf-1-dependent pathway, which results in the phosphorylation of the inward rectifier K+ channel protein.

Animals↗

Suppressive effect of vagal afferents on the activity of the trigeminal spinal neurons related to the jaw-opening reflex in rats: involvement of the endogenous opioid system.

The purpose of the present study is to test the hypothesis that via the endogenous pain control system, vagal afferent input modulates the activity of the trigeminal spinal nucleus oralis (TSNO) related to the tooth pulp (TP)-evoked jaw-opening reflex (JOR). Extracellular single-unit recordings were made from 36 TSNO units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram (dEMG) signal in 26 pentobarbital-anesthetized rats. The activity of 36 TSNO neurons and the amplitude of the dEMG increased proportionally during 1.0-3.5 times the threshold for JOR. Some of these neurons (4 out of 5) were also excited by chemical stimulation (bradykinin, 1-2 microl, 1 mM) of TP. In 31 out of 36 TSNO neurons (86%), their activities during tooth pulp stimulation were suppressed by conditioning stimulation of the right vagus nerve. The suppressive effect of vagal afferent stimulation occurred at conditioning-test intervals of 20-150 ms after the onset of the stimulation, and its maximal suppressive effect occurred at approximately 50 ms. The mean time course of this suppressive effect paralleled that of the dEMG. After administration of naloxone (0.5 and 1.0 mg/kg, i.v.), an opiate receptor blocker, the suppressive effect on the activity of TSNO neurons (6 out of 8) was significantly attenuated at the conditioning-test interval of 50 ms compared to the control (p < 0.01). These results suggested that vagal afferent input inhibits nociceptive transmission in the TSNO related to TP-evoked JOR and this inhibitory effect may occur via the endogenous opioid system in rats.

Afferent Pathways↗

Pulse exposure of cultured rat neurons to aluminum-maltol affected the axonal transport system.

Although chronic aluminum neurotoxicity has been well established, the mechanism of the toxicity has not been elucidated yet. In order to simplify the study of the aluminum neurotoxicity, we employed the pulse exposure of cultured rat cortical neurons to 250 microM aluminum-maltol for 1 h at the early stage (6 h after plating), which resulted in abnormal distribution of neurofilament L (NFL) and fast axonal transported proteins, whereas the axonal transport of tubulin, actin, and clathrin were not impaired. Otherwise, the pulse exposure of neurons at the late stage (4 days after plating) to the same concentration of aluminum-maltol did not affect the cell morphology and the distribution of NFL. The pulse exposure of cultured neurons to aluminum-maltol at the early stage might affect the axonal transport system of NFL and fast axonal transported proteins.

Actins↗

Levels of tau phosphorylation at different sites in Alzheimer disease brain.

The microtubule-associated protein tau is abnormally hyperphosphorylated in Alzheimer's disease (AD) brain. To date, 21 phosphorylated sites of tau have been identified. In the present study the levels of phosphorylation at Ser199/Ser202, Thr231/Ser235, Ser262/Ser356 and Ser396/Ser404 of tau in AD brain homogenate and its 100,000 x g supernatant were determined using radioimmuno-dot-blot assay. In homogenate, Ser199/Ser202 and Ser262/Ser356 were phosphorylated to similar level and were more phosphorylated than Thr231 or Ser396/Ser404. In supernatant, there was no significant difference in phosphorylated tau level among the investigated sites except for Thr231/Ser235 which was least phosphorylated. These results suggest that Ser199/Ser202 and Ser262/Ser356 are major sites of phosphorylation of tau in AD brain.

Aged↗