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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 1,639 records · Page 91Linked to original sources

Effect of modification of enkephalin C-terminal functions on affinity selection of opioid receptors.

Enkephalin analogs with various C-terminal modifications have been synthesized to evaluate the corresponding structural elements in the opioid receptors. The carboxyl group of the C-terminal leucine5 or glycine5 was converted into the mercaptomethyl (-CH2SH) and hydroxymethyl (-CH2OH) groups, starting from leucinthiol or leucinol for Leu5-derivatives and from cysteamine or ethanolamine for Gly5-derivatives. Interactions of synthetic peptides with the opioid receptors were examined by the radioligand receptor binding assays using rat brain and tritiated enkephalin analogs. The data suggest that the C-terminal carboxyl group in enkephalins is important, but not electrostatically, for interaction with delta-opioid receptors. With leucinthiol-enkephalin in biological assays which examine its inhibitory activity for electrically stimulated contractions of isolated smooth muscle, it was found that the reactive thiol group exists in the mu receptors present in the guinea pig ileum. Leucinthiol-enkephalin became bound covalently to this receptor-thiol group via disulfide formation after prolonged incubation.

Affinity Labels↗

Heme-biosynthetic enzyme activities and porphyrin accumulation in normal liver and hepatoma cell lines of rat.

The activities of four heme-biosynthetic enzymes, delta-aminolevulinic acid (ALA) synthase, ALA dehydratase, porphobilogen (PBG) deaminase, and ferrochelatase, were studied in five epithelial cell lines of normal rat liver origin (RL, RLC-10, RLC-24, M, Culb-TC) and five cell lines derived from Yoshida ascites hepatoma (JTC-1, JTC-2, JTC-15, JTC-16, JTC-24). The JTC series of hepatoma-derived cell lines exhibited decreased ALA synthase activity and increased ALA dehydratase activity, although the activities of all four enzymes and the Km values for their respective substrates varied widely from one cell line to another, a finding suggesting that specific regulatory mechanisms for porphyrin metabolism might operate in each cell type. M cells, which were transformed by 4-dimethylaminoazobenzene in vitro, gave the most abnormal Km values of heme-biosynthetic enzymes among all the cell lines studies, and were found to accumulate hematoporphyrin derivative (HpD).

5-Aminolevulinate Synthetase↗

Effects of multiple dosing of phenacetin in the micronucleus test.

As a part of the international cooperative study to identify the most sensitive regimen in the micronucleus test, phenacetin was given i.p. to male CD-1 mice at doses of 37.5, 75, 150, 300, 400, and 600 mg/kg once, twice, thrice or four times and the bone marrow cells were harvested 24 h after the final dosing. Positive responses were seen at 600 mg/kg after single and triple dosing and at 400 and 600 mg/kg after double dosing. No dose level gave a positive response after quadruple dosing. A repeated-dosing effect was detected at double and triple dosing. Although triple dosing gave the highest magnitude of micronuclei at 600 mg/kg, double dosing showed a sufficient sensitivity and was more convenient from the viewpoint of selecting a suitable test dose and carrying out the micronucleus test.

Animals↗

Effect of age on short-wavelength sensitive cone electroretinogram and long- and middle-wavelength sensitive cone electroretinogram.

Using a light-emitting diode (LED) built-in contact lens electrode, we studied the effect of age on short-wavelength sensitive cone electroretinograms (S-cone ERG) and long- and middle-wavelength sensitive cone ERGs (LM-cone ERG). We recorded ERGs in 31 pseudophakic subjects to avoid the effect of yellowing in the human crystalline lens. The intensities of our stimuli were on the asymptote of the intensity-response curve. Linear regression analysis against age was carried out on the S-cone ERG b-wave, and the LM-cone ERG a-, b-, and d-waves. We found significant age-dependent reduction in the amplitude of the S-cone ERG b-wave, and the LM-cone ERG a- and d-waves, significant prolongation in the peak time of the S-cone b-wave and the LM-cone ERG b-wave, significant increase in the b/a ratio of the LM-cone ERG, but no significant age correlation between the LM-cone ERG a-wave and the amplitude of the b-wave. Our results provide evidence that age-related changes in S- and LM-cone systems begin in early adulthood in the human eye. A significant increase in the b/a ratio suggests that off-bipolar cells are more vulnerable to aging than on-bipolar cells.

Adult↗

Amplitude decrease of photopic ERG b-wave at higher stimulus intensities in humans.

PURPOSE: The b-wave of the human photopic electroretinogram (ERG) elicited by a short-flash increases in amplitude with increasing stimulus intensities at lower stimulus levels, but then decreases at higher stimulus intensities. The purpose of the present study was to explore this phenomenon in more detail, using short- and long-flash stimuli. METHODS: The intensity-response functions of the b-wave elicited by short- and long-flashes were compared from threshold to higher stimulus intensities in 5 normal subjects. Short- and long-flash ERGs were elicited under rod-saturating background levels using white light-emitting diodes built into a contact lens electrode. RESULTS: Whereas the amplitude of the short-flash b-wave decreased at higher intensities, the amplitude of the long-flash ERG b-wave did not decrease but plateaued. The long-flash ERG d-wave or OFF-response decreased at higher stimulus levels as did the short-flash elicited b-wave. CONCLUSIONS: Because it is widely accepted that the b-wave and the OFF-response d-wave interact to produce a single positive response, our results suggest that the decrease in the b-wave amplitude at high stimulus intensity is caused by the decrease of the d-wave at the higher stimulus intensities.

Adaptation, Ocular↗

Effects of reactive oxygen species on intracellular calcium in bovine tracheal epithelium: modulation by nitric oxide.

We studied the effects of reactive oxygen species (ROS) on intracellular Ca2+ concentration ([Ca2+]i) and their possible modulation by nitric oxide (NO) in fura-2-loaded cultured bovine tracheal epithelium. Hypoxanthine (HX) and xanthine oxidase (XO), which generate superoxide anion (O2-) and hydrogen peroxide (H2O2), dose dependently increased [Ca2+]i. The increase in [Ca2+]i was reduced in the presence of superoxide dismutase (SOD, 200 U/mL) and catalase (200 U/mL) by 29% and 43%, respectively. The iron chelator o-phenanthroline and the hydroxyl radical (.OH) scavenger dimethylthiourea (DMTU) more potently inhibited the response of [Ca2+]i. H2O2-derived .OH generated by the Fenton reaction caused a marked [Ca2+]i elevation, but exogenous H2O2 did not. Sodium nitroprusside (100 microM), an NO donor, potentiated HX-XO-induced [Ca2+]i rise by 50%, an effect that was abolished in the presence of SOD or DMTU. These results suggest that .OH formed by interaction of O2- and H2O2 in the presence of iron may play a major role in the HX-XO-induced disruption of airway epithelial Ca2+ homeostasis, and that NO potentiates ROS-induced [Ca2+]i response, presumably by reacting with O2- and producing .OH.

Animals↗

Hierarchical differences in body composition of professional Sumo wrestlers.

The body composition of 36 professional Sumo wrestlers and 39 collegiate male students were assessed densitometrically. The means of body weight, BMI and %fat for Sumo wrestlers were 117.1 kg, 36.5 and 26.2%, extraordinarily large compared with untrained men (p < 0.001). Results of the analysis of variance of divisions of Sumo wrestlers revealed significant differences in body weight, fat-free mass, fat mass, BMI, fat-free mass index (FFM/height2) and fat mass index (FM/height2). For the visual expression of the hierarchical differences of body composition, fat mass index and fat-free mass index of the wrestlers in various leagues were plotted on a body composition chart. Wrestlers in the Sekitori division had significantly larger fat-free mass index scores in comparison with wrestlers from the lower divisions who share a common area of the chart. The cut-off point of fat-free mass index which divided Sekitori wrestlers from other wrestlers is approximately 30 and this value may be one of the anthropometrical indications of whether or not a Sumo wrestler is destined to be successful.

Adipose Tissue↗

Gene delivery systems using the Sendai virus.

Fusogenic liposome (FL) is a delivery system that can transfer encapsulated materials into living cells directly through membrane fusion. FL is a promising approach for gene therapy because it can deliver various genetic materials much more efficiently than other non-viral vectors without damaging the cell. FL-mediated gene transfer consists of two independent membrane fusion phenomena; generation of a FL by fusing a Sendai virus (SV) particle with a simple liposome encapsulating DNA, and successive fusion of the FL with cell membrane. The former requires viral F protein but no other special molecule on the liposomal membrane, whereas the latter may require the receptor (sialic acid) and unidentified assistant molecule(s) on the cell membrane. Further analysis suggests that these assistant molecule(s), not the receptor, may control the fusion and govern the cell specificity of FL-mediated delivery. This review has described a detailed analysis of these fusion phenomena and discussed possible applications of FL-mediated gene delivery to human gene therapy.

Genetic Therapy↗

Extramedullary plasmacytoma of the sinonasal cavities: CT evaluation.

Computed tomography was performed in four patients with solitary extramedullary plasmacytoma of the nasal cavity and paranasal sinuses. Two tumors originated in the nasal cavity, one in the maxillary sinus, and one in the frontal sinus. Soft tissue mass(es) was seen in all patients. Bone destruction was apparent in only two patients. It seems possible to rule out carcinomas in such patients with no or subtle bony destruction. Computed tomography was also helpful for planning radiation therapy.

Adult↗

Anti-obesity and anti-diabetic effects of mazindol in yellow KK mice: its activating effect on brown adipose tissue thermogenesis.

1. The anti-obesity and anti-diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57Bl control mice. 2. The study compound was fed through a gastric tube at a rate of 1 or 2 mg/kg per day (0.01 mol/L HCl as control) for 2 weeks. The following parameters were compared in treated and control animals: bodyweight, food intake, white adipose tissue (WAT) weight, brown adipose tissue (BAT) weight and its thermogenesis, noradrenaline (NA) turnover, blood glucose and serum insulin levels and glucose transporter 4 (GLUT4). 3. Furthermore, bodyweight loss of mice pair-fed the same amount of food as the mazindol-treated mice for 2 weeks was measured. 4. Mazindol significantly decreased food intake and significantly increased guanosine-5'-diphosphate-binding in BAT mitochondria and NA turnover in BAT in both yellow KK and C57Bl groups. The amounts of WAT in subcutaneous, mesenteric and retroperitoneal regions and bodyweights were significantly decreased in both groups. Bodyweight loss in mice pair fed with the mazindol-treated groups was approximately 70% compared with that in the mazindol-treated groups. Furthermore, mazindol decreased the levels of blood glucose and serum insulin during the glucose overloading test in yellow KK mice, but it did not influence the GLUT4 protein concentration in WAT and muscle. 5. These observations suggest that mazindol possesses both an anti-obesity action, due to the inhibition of appetite as well as the activation of BAT thermogenesis via increased NA turnover in BAT, and an anti-diabetic action. Consequently, mazindol may be useful for the treatment of obesity as well as non-insulin-dependent diabetes mellitus in obese persons.

Adipose Tissue↗

Enhancement of interleukin-2-induced lymphokine-activated killer activity by interleukin 7 against autologous human renal cell carcinoma.

Adjuvant immunotherapy with interferons and/or interleukin 2 (IL-2) is widely used for advanced kidney cancer. However, the results are not satisfactory so far. The purpose of this study is to evaluate the inducible activity of lymphokine-activated killer (LAK) cells against autologous human renal cell carcinoma. The effect of interleukin 7 (IL-7) on IL-2-induced LAK activity was assessed by the autologous assay system which we have established. Peripheral blood lymphocytes from patients with renal cell carcinoma were stimulated with IL-2 and/or IL-7, and tested for antitumor activity against autologous renal cell carcinoma. In all 10 cases tested, IL-7 alone induced LAK activity. Moreover, IL-2-induced LAK activity was augmented by the concomitant addition of IL-7. Flow cytometry revealed an increase in IL-2-receptor-positive lymphocytes following incubation with IL-7. These results suggest that combination therapy using IL-2 and IL-7 may be a useful treatment for patients with advanced renal cell carcinoma.

Aged↗

Pharmacokinetics and lipid-lowering effect of fluvastatin in hypercholesterolaemic patients on maintenance haemodialysis.

Patients undergoing haemodialysis are predisposed to serum lipid abnormalities that can accelerate the development of atherosclerosis. Serum lipid levels must therefore be controlled over a long period. For patients with reduced renal function (including dialysis patients), special attention must be paid to hyperlipidaemia therapy, particularly drug selection. In this study, 30 mg/day fluvastatin was administered orally to five patients receiving maintenance haemodialysis. Their serum lipid levels and blood biochemistry were monitored during the 6 months of fluvastatin administration, and the pharmacokinetic parameters calculated. The therapeutic efficacy and safety of fluvastatin were demonstrated in this patient group. Furthermore, fluvastatin is not influenced by the dialysis membrane and does not accumulate in haemodialysis patients with hyperlipidaemia.

Anticholesteremic Agents↗

[Liver transplantation from living related donors]

OBJECTIVES: To present the experience with the first 12 living related liver transplants performed at Hospital Sírio-Libanês in São Paulo. METHODS: The donors were the fathers (6) and the mothers (6) with age ranging from 30 to 48 years. All candidates for donation were submitted to a full informed consent form, clinical and radiological evaluation and had blood withdrawn for autotransfusion. Recipient age ranged from 7 months to 10 years whereas recipient weight varied from 6.3 to 34 kg. Six patients were considered as high risk due to complications of advanced liver disease and were submitted to urgent transplantation. RESULTS: Mean donor hospital stay was 10 days with no mortality. Technical complications were observed in 4 recipients. Seven patients presented at least one episode of bacterial, viral or fungal infection. One or more biopsy proven rejection episodes were disclosed in 7 patients. Overall recipient survival was 67%, being 83% for elective cases and 50% for urgent cases. Long term follow up ranged from 8 to 25 months. Seven out of 8 survivors present excellent quality of life and normal liver function. The other patient is currently under reduced immunosuppression due to Epstein-Barr virus infection.CONCLUSIONS: These results demonstrate the safety and viability of living related liver transplantation which, in face of the current donor scarcity, should be considered as a valid option for the treatment of children with end stage liver disease.

Journal Article↗

Zizyphi fructus, a constituent of antiasthmatic herbal medicine, stimulates airway epithelial ciliary motility through nitric oxide generation.

The effects of Zizyphi fructus, a major constituent of Chinese anti-asthmatic herbal medicine, on ciliary motility and nitric oxide (NO) generation in canine cultured tracheal epithelium were studied by the microphoto-oscillation method and the specific amperometric method, respectively. Addition of Zizyphi fructus at 100 micrograms/mL rapidly increased ciliary beat frequency (CBF), an effect that was inhibited by NG-nitro-L-arginine methylester (L-NAME) but not by NG-nitro-D-arginine methylester (D-NAME), and this inhibition was reversed by L-arginine but not by D-arginine. Immersion of the NO-selective electrode in the medium bathing tracheal epithelial cells showed a baseline current of 21.3-60.4 pA, which corresponded to NO concentration ([NO]) at 34.4 +/- 7.8 nM. Zizyphi fructus caused a concentration-dependent increase in [NO], the maximal increase from the baseline [NO] level and the concentration of Zizyphi fructus required to produce a half-maximal effect (EC50) being 107 +/- 14 nM (p < .001) and 7.2 +/- 2.9 micrograms/mL, respectively. These results suggest that Zizyphi fructus enhances airway ciliary motility and that this effect is exerted through the stimulation of epithelial NO generation.

Animals↗

Combined effects of hepatic arterial embolization using degradable starch microspheres (DSM) in hyperthermia for liver cancer.

Regional hyperthermia with a radiofrequency capacitive heating apparatus in combination with hepatic arterial embolization with degradable starch microspheres (DSM) was performed in 20 primary and six metastatic liver cancer patients. Efficacy was assessed primarily with regard to the improvement in heating efficiency. An angiocatheter was inserted into the hepatic artery in order to determine the DSM dosage adequate to arrest blood flow. The temperature rise in the tumours after heating alone and after heating combined with DSM embolization was compared. The maximum temperature and initial temperature rise within tumours were significantly improved by the combination therapy. Local tumour response could be evaluated in 10 primary and three metastatic liver cancer patients and tumour reduction over 50% was obtained in 40% and 33% respectively. Abdominal pain, nausea and vomiting, presumably due to reflux of the DSM, were experienced by several patients. In three patients heating could not be continued. However, all the symptoms were transient and responsive to symptomatic treatment, and no significant late complications were observed. Hepatic arterial embolization with DSM for liver tumours is considered effective and safe when combined with regional hyperthermia.

Adult↗