Biomedical subjects

Y Kinouchi

Publications and source records attributed to Y Kinouchi.

At least 55 records · Page 3Linked to original sources

PubMed1996

A novel method for the preclinical assessment of rectal irritation.

The purpose of this study concerns a novel method for preclinical assessment of rectal irritation caused by suppositories introduced into the rectum. Rectal irritation was assessed by the balloon method in fasting conscious rats. This method is based on measuring rectal contractions due to possible irritation caused by the presence of drugs and adjuvants in the suppository. In control experiments (vehicle only), significant rectal contractions were not observed in a range of pH 1.5-11.0 and osmotic pressure 70-2000 mOsm kg-1 H2O, respectively. On the other hand, strong contractions were observed after rectal administration of an aqueous solution of 50% glycerin, 100 mM sodium caprate or 25 mM sodium cholate. The intensity of contraction after rectal administration of sodium caprate or sodium cholate was dependent on the concentration in the dosing solution. In addition, the effect of sodium caprate and sodium cholate on rat rectal mucosa was investigated by optical light microscopy. Although slight or moderate alteration such as the presence of mucinous substance in lumen and congestion, oedema and haemorrhage of the rectal membrane 20 min after rectal administration, there was no major damage to the rectal mucosa. There was a correlation between the median score for mucinous substance in lumen and mean intensity of rectal contraction. For comparative purposes, defecating sensations, pain, itch, burning sensations, and awareness of the presence of a foreign body after administration of suppositories containing 0, 1, 2 and 4% sodium caprate were examined in eight healthy volunteers. The defecating sensation in the human subjects correlated with the intensity of rectal contraction in rats. The results suggest that rectal contraction in conscious rats could be a useful index for prediction of a defecating sensation in man.

Adult↗

PubMed1996

[Characteristics of enterotoxigenic Escherichia coli and E. coli harboring enteroaggregative E. coli heat-stable enterotoxin-1 (EAST-1) gene isolated from a water-borne outbreak].

A water-borne outbreak occurred in A Town in Akita prefecture on March 1995. Enterotoxigenic Escherichia coli (ETEC) strains were isolated from 6 of 13 feces of patients with food poisoning disease and from 1 of 4 drinking water samples. In addition, E. coli strains harboring Enteroaggregative E. coli (EAggEC) heat-stable enterotoxin-1 (EAST-1) gene were isolated from 5 of 13 patient's feces and 1 feces sample obtained from the septic tank. Both of the E. coli strains were isolated from the 3 patient's feces, suggesting that this outbreak was a mixed infectious case. All of the ETEC strains possessed both heat-stable enterotoxin (ST) and EAST-1 genes and their serotype was O148:H28. The EAST-1 gene was detected on a ca. 80 kb plasmid by a southern blot analysis using EAST-1 DNA probe in the 5 of 7 ETEC strains. The southern blot analysis suggested that the location of the EAST-1 gene was genome in the rest of the 2 ETEC strains. A southern blot analysis using ST DNA probe also suggested that the location of the ST gene was genome in all of the ETEC strains. On the other hand, all of the 6 E. coli strains harboring EAST-1 gene could not be serotyped with commercially available OH sera. The location of the EAST-1 gene in all of the isolates was suggested to be genome by the southern blot analysis. All of the isolates lacked aggA gene which has been demonstrated to be involved in expression of aggregative adherence phenotype in EAggEC, suggesting that the EAST-1 gene-harboring strains isolated in this case were distinct from EAggEC. These results indicated that the EAST-1 gene was also harbored by E. coli strains distinct from EAggEC. In addition, a possibility was also suggested that the EAST-1 gene might be a transposon, as well as ST gene. Further study should be conducted in order to elucidate the significance of EAST-1 as a vilurence factor of diarrheagenic E. coli.

Bacterial Toxins↗

PubMed1996

[Enteropathogenic Escherichia coli strains harboring enteroaggregative Escherichia coli (EAggEC) heat-stable enterotoxin-1 gene isolated from a food-borne like outbreak].

A food-poisoning outbreak occurred in G Town in Minami-Akita District, Akita Prefecture on 16 January 1995. As the causative agent of the outbreak, Enteropathogenic Escherichia coli (EPEC) O126:NM were isolated. The isolates showed the same plasmid profile and antibiotic susceptibility patterns suggesting that the EPEC strains originated from same infectious source. The isolates lacked eae and EAF genes which were considered to play a significant role in the diarrheagenic mechanism of EPEC. On the otherhand, the isolates possessed Enteroaggregative E. coli (EAggEC) heat-stable enterotoxin-1 (EAST-1) gene, though they did not possess the agg A gene in which the coded structural subunit of Aggregative adherence fimbriae 1 (AAF/1) has been demonstrated to be involved in the expression of ability for EAggEC to adhere to cultured cells in aggregative pattern, indicating that the EPEC strains apparently differed from EAggEC. These data suggested that EAST-1 showed its enterotoxic activity to human, and that EPEC represented multiple category of E. coli strains with different diarrheagenic mechanism, in which both eae and EAST-1 might be involved.

DNA Primers↗

PubMed1996

Effect of some amino acids on the rectal irritation caused by sodium caprate in conscious rats.

The effects of some amino acids such as L-glutamine (Gln), L-arginine (Arg) and L-methionine (Met) on rectal irritation caused by sodium caprate were studied in rats. Rectal irritation was assessed by the balloon method in fasting conscious rats. This method is based on measuring rectal contractions due to possible irritation caused by the presence of drugs and/or adjuvants in the rectum. Strong contractions were observed after rectal administration of an aqueous solution of 100 mM sodium caprate. However, the presence of Gln, Arg or Met (100 mM) in sodium caprate (100 mM) solution resulted in a significant decrease in the intensity of the rectal contraction caused by sodium caprate. The rectal absorption-promoting effect of sodium caprate on 6-carboxyfluorescein (6-CF) was examined following administration with amino acids in rats. The absorption of 6-CF was not influenced by the concurrent administration of amino acids. In addition, the rectal tissue interaction of sodium caprate, with or without Gln, was examined. The concentration of sodium caprate in rectal tissue was reduced by the presence of Gln.

Amino Acids↗

PubMed1996

Detection of herpes simplex virus DNA in tear fluid of stromal herpetic keratitis patients by nested polymerase chain reaction.

The value of the polymerase chain reaction (PCR) in the diagnosis of stromal herpetic keratitis was examined using tear fluid specimens; the sensitivity of the nested PCR method in detecting the herpes simplex virus (HSV) genome was 1 plaque-forming unit/mL. PCR assay of 72 tear samples from the eyes of 15 patients with stromal herpetic keratitis detected the HSV genome in 5 (33.3%). No positive band was detected in 20 tear samples from both eyes of 10 healthy volunteers. Seven of 38 tear samples (18.4%) and 1 of 34 samples (2.9%) collected from the diseased eye and the contralateral normal eye, respectively, produced positive results; the difference in rates was statistically significant (P < 0.05). The positive rate of samples collected from the diseased eye during an active phase was 16.0% (4 of 25 samples); in the quiescent phase, 23.1% (3 of 13 samples); the difference was not significant (P = 0.45). In HSV genome-positive cases, the average number of tear collections needed to detect the HSV genome was 3.3. Results indicate that PCR assay of tear fluid provides valuable information for the diagnosis of stromal herpetic keratitis, and that repeated tear samples should be collected regardless of the phase of the phase of disease activity.

Administration, Topical↗

PubMed1995

Blood flow velocity in the common carotid artery in humans during graded exercise on a treadmill.

Cerebral blood volume flow and flow velocity have been reported to increase during dynamic exercise, but whether the two increase in parallel and whether both increases occur as functions of exercise intensity remain unsettled. In this study, blood flow velocity in the common carotid artery was measured using the Doppler ultrasound method in eight healthy male students during graded treadmill exercise. The exercise consisted of stepwise progressive increases and decreases in exercise intensity. The peak intensity corresponded to approximately 85% of maximal oxygen consumption. During this exercise, the heart rate (fc), mean blood pressure (BP) in the brachial artery and mean blood flow velocity (vcc) in the common carotid artery increased as functions of exercise intensity. At the peak exercise intensity, fc, BP and vcc increased by 134.5%, 20.5% and 51.8% over the control levels before exercise (P < 0.01), respectively. The resistance index (RI) and pulsatility index (PI) were determined from the velocity profile and were expected to reflect the distal cerebral blood flow resistance. The RI and PI increased during the graded exercise, but tended to decrease at the highest levels of exercise intensity. As vcc increased with increases in exercise intensity it would be expected that cerebral blood flow would also increase at these higher intensities. It is also suggested that blood flow velocity in the cerebral artery does not proportionately reflect the cerebral blood flow during dynamic exercise, since the cerebral blood flow resistance changes.

Blood Flow Velocity↗

PubMed1995

Electrical properties of extracted rat liver tissue.

We attempted to investigate the process of ischemia-induced disturbances in the rat liver, employing the electrical bio-impedance technique. The electrical bio-impedance was measured continuously over 6 h by the 4-electrode method, at various incubation temperatures, in six liver samples extracted from male Wistar rats. The electrical properties of biological tissues can be expressed in terms of three parameters: extracellular resistance (Re), intracellular resistance (Ri) and cell membrane capacitance (Cm). These three parameters were calculated from the measured values of the electrical impedance by the curve-fitting technique, using a computer program. The Re value increased rapidly after the rat livers were extracted, and then decreased slowly. The Re value reached a peak after about 13 min at 36 degrees C, and then decreased slowly, becoming constant after 3 h. There was a negative correlation between the Tmax of Re (the time when Re reached a maximum) and the incubation temperature (R = -0.973, P < 0.001). The Ri value decreased once in the early stage after extraction, followed by almost no change and then an increase after 4 h at 36 degrees C. The Cm showed a similar pattern of change to the Re value, and a negative correlation was also found between the Tmax of Cm and the incubation temperature (R = -0.969, P < 0.001). The increase in the Re and Cm values, and the decrease in the Ri value for quite long periods after the blood flow has stopped, suggest an increase in the resistance of extracellular fluid due to a decrease in its volume, an increase in cell membrane capacitance due to cell swelling, and a decrease in cellular fluid resistance due to an increase in its volume. The time when the Cm value decreases rapidly after an initial gradual decrease after the peak corresponds well with the time when the Ri value begins to increase, from which it is estimated that cell lysis proceeds and that the flow of extracellular fluid into the cell begins at this time. The findings of this study suggest the possibility of estimating the changes in liver tissue or the tissue structure due to ischemia.

Animals↗

PubMed1995

An experimental study of conductive heating using a concentric double-electrode applicator.

With hyperthermia for treatment of superficial tumors in mind, a prototype applicator with two electrodes arranged concentrically on a disk was designed for efficient local heating, and a basic heating test was carried out. Frequencies as low as 200 kHz were used in order to simplify the configuration of the power device. The applicator consists of two electrodes, a circular inner electrode and another looped outer electrode, arranged concentrically. Water was passed through the applicator as a cooling mechanism; it was placed in direct contact with the target tissue to be heated and then charged with electricity. In the heating test using a phantom, oval hot spots were noted below the inner electrode. Using cooling water at 3 degrees C and 8.2 W, an isothermal line of 45 degrees C was located at a 5-mm radius circle around the central axis with 9 mm depth. A similar temperature distribution map was obtained in heating tests on the thigh muscle of a mongrel adult dog. The temperature distribution maps obtained from these tests corresponded closely with the results of theoretical analysis carried out according to the finite-element method. Since a comparatively low frequency was employed for this applicator the power device was simplified, which made adequate heating possible with low electric power. The temperature distribution map indicated that efficient local heating of superficial tumors could be achieved.

Electrodes↗

PubMed1995

Exercise-induced changes in R wave amplitude and heart rate in normal subjects.

An intermittent exercise protocol on a treadmill was used to examine six healthy subjects, and a steady protocol was applied to three of the subjects before and after short-term training. The peak blood velocity in the common carotid artery increased by 73.1% during the intermittent protocol and recovered to resting level within 3 minutes, while the heart rate (HR) remained high even 5 minutes after exercise. R wave amplitude (RWA) increased significantly from 1.40 +/- 0.39 mV at rest to 1.59 +/- 0.33 mV (P < .05) immediately after the start of walking, and decreased gradually to 1.46 +/- 0.36 mV (P < .05) during 3 minutes of walking. Thus, it decreased significantly to 1.31 +/- 0.40 mV (P < .01) during the interphase from exercise to rest, and increased again during recovery or rest periods in the intermittent protocol. The results suggest that an increase in the venous return per heart beat at the start of walking induces the increase in RWA, and that its abrupt decrease at the end of walking induces the decrease in RWA. Subjects with a higher HR response and recovery slopes have smaller abrupt changes in RWA at the interphases between rest and walking. The gradual decrease in RWA during walking may be related to a gradual increase in HR and a gradual decrease in systemic peripheral resistance, and the gradual increase in RWA after walking may be related to a gradual decrease in HR and a gradual increase in systemic peripheral resistance.

Adult↗

PubMed1995

Altered leukotriene B4 metabolism in colonic mucosa with inflammatory bowel disease.

BACKGROUND: omega-Oxidation is regarded as the major pathway for leukotriene B4 (LTB4) metabolism. Very little is known about it in colonic mucosa with inflammatory bowel disease (IBD). METHODS: We investigated the metabolic ratio of omega-oxidation to LTB4 biosynthesis in colonic mucosa from patients with IBD and control subjects. After incubation of colonic mucosa with 14C-arachidonic acid and ionophore A23187, we separated LTB4 and its omega-oxidative metabolites by high-performance liquid chromatography. RESULTS: The rate of LTB4 omega-oxidation was comparable to the rate of its biosynthesis. The metabolic ratio was significantly decreased in inflamed mucosa with ulcerative colitis. CONCLUSIONS: LTB4 omega-hydroxylase activity is an important factor in regulating LTB4 level in colonic mucosa, and the increased LTB4 level in inflamed mucosa with IBD, especially ulcerative colitis, is caused by decreased LTB4 omega-hydroxylase activity and increased 5-lipoxygenase activity.

Adolescent↗

PubMed1994

5-Aminosalicylic acid inhibits leukotriene B4 omega-hydroxylase activity in human polymorphonuclear leukocytes.

omega-Oxidation is regarded as the major pathway for the metabolism and inactivation of leukotriene B4 (LTB4). To investigate the action of 5-aminosalicylic acid (5-ASA) on LTB4 omega-hydroxylase activity, we incubated human polymorphonuclear leukocytes (PMNLs) with 3H-labeled LTB4 after pre-incubation with various concentrations of 5-ASA. omega-oxidation metabolites were separated by high performance liquid chromatography and each radioactivity was measured by a liquid scintilation counter. LTB4 omega-hydroxylase activity was inhibited by 5-ASA in a concentration-dependent fashion. The 50% inhibitory dose was about 50 mumol/l, which is within the concentration range found in the colonic mucosa. Our findings may be valuable in elucidating the potentially critical aspect of 5-ASA treatment in ulcerative colitis (UC).

Aminosalicylic Acids↗

PubMed1994

Effects of fluidity and vesicle size on antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin.

The effects of fluidity and vesicle size on the antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin, an anthracycline antitumor drug, were investigated in Yoshida sarcoma-bearing rats. Liposomes composed of egg phosphatidylcholine (EPC) or hydrogenated egg phosphatidylcholine (HEPC), cholesterol and dicetyl phosphate in a molar ratio of 5:4:1 were injected intravenously into rats 5 d after subcutaneous inoculation of Yoshida sarcoma. At non-effect dosage in free drug, HEPC-liposomes with a diameter of 58 or 142 nm showed the greatest inhibitory effect against Yoshida sarcoma among liposomes tested, whereas larger ones (272 nm) had weaker effect. Small EPC-liposomes (57 nm) had no effect. Larger HEPC-liposomes (especially 142 nm) greatly decreased the number of peripheral white blood cell compared with free drug at the same dose, indicating relatively strong myelosuppressive toxicity. However, small EPC- and HEPC-liposomes with a diameter of 57 and 58 nm, respectively, showed toxic effects comparable to that of free drug. Examination of the dose-dependency of therapeutic effects and toxicity indicated encapsulation of daunorubicin in the small HEPC-liposomes to enhance the therapeutic index about 3 times that of free drug. These findings indicate the possibility of using small HEPC-liposome as a drug carrier for targeting solid tumors.

Animals↗

PubMed1994

Application of electrical impedance analysis for diagnosis of a pulmonary mass.

The electrical impedance of a pulmonary mass was measured in 53 patients of whom 44 had primary lung cancer, 5 had metastatic lung tumor, and 4 had organizing pneumonia. Because biologic tissue can be regarded, electrically, to consist of extracellular resistance (Re), intracellular resistance (Ri), and the electrical capacitance of the cell membrane (Cm), these three parameters were calculated from the measured electrical impedance of tissue by a curve-fitting technique using a computer program. The Re of lung tissue was significantly greater (p < 0.01) and the Cm of lung tissue was significantly less (p < 0.01) than that of a pulmonary mass. The Re of malignant tumors (both lung cancer and metastatic tumors) was significantly greater (p < 0.01) and the Cm of malignant tumors was significantly less (p < 0.01) than that of organizing pneumonia. With this information, we used a biopsy needle to diagnose nine intrathoracic lesions. This technique additionally allowed us to confirm the proximity of the needle tip of the mass. The electrical impedance of the lung mass was measured through the biopsy needle using a modified impedance analysis system before the biopsy was performed. There were no false-negative results, and one false-positive result. The rapid measurement of the electrical impedance of a pulmonary mass, preoperatively, may be of value in the clinical evaluation of a pulmonary mass both by facilitating needle guidance and by permitting diagnosis based on electrical impedance.

Aged↗

PubMed1994

Flow velocity in carotid artery in humans during immersions and underwater swimming.

Heart rate and flow velocity in the common carotid artery were examined on eight subjects in various underwater conditions. The heart rate decreased more markedly during whole-body immersion than during head-out immersion. The end-diastolic flow velocity and the flow-velocity integral in a cardiac cycle during whole-body immersion increased more markedly than during head-out immersion. Differences in heart rate and flow velocity were not detected between sitting and prone positions in whole-body immersion. Heart rate increased at the beginning and after underwater swimming. The peak systolic flow velocity increased significantly after the end of underwater swimming. The flow-velocity integral in a cardiac cycle decreased during underwater swimming, but in a minute did not change significantly. These results suggest that facial immersion is important in eliciting pronounced carotid artery flow-velocity response in addition to the heart-rate response and that underwater exercise influences these responses. However, underwater posture apparently does not influence them.

Adult↗

PubMed1993

Effects of seven months' exposure to a static 0.2 T magnetic field on growth and glycolytic activity of human gingival fibroblasts.

Human gingival fibroblasts in confluent cultures were continuously exposed to a static 0.2 T magnetic field for 6 or 8 months. Culture flasks were not changed during the exposure, but culture medium was renewed. After dilution and mixing of the cultures surviving intact, field-exposed and sham-exposed cultures received further field- or sham-exposure on Sm-Co blocks. Rate of cell proliferation, histogram of the nuclear DNA content, rates of lactate production and glucose consumption and the ATP content were determined and cell morphology was investigated by both light- and electron-microscopy. Results show no marked differences between exposed and control cells.

Adenosine Triphosphate↗

PubMed1993

Changes in carotid blood flow and electrocardiogram in humans during and after walking on a treadmill.

Blood flow velocity in the common carotid artery and the electrocardiogram were measured simultaneously by telemetry in seven male subjects during 20-min walking on a treadmill at an exercise intensity corresponding to a mean oxygen uptake of 26.0 (SD 2.9) ml.kg-1.min-1. The mean cardiac cycle was shortened from 0.814 (SD 0.103) s to 0.452 (SD 0.054) s during this exercise. Of this shortening, 73% was due to shortening of the diastolic period and 27% to shortening of the systolic period. In the relatively small shortening of the mean systolic period [from 0.377 (SD 0.043) s to 0.268 (SD 0.029) s], the isovolumetric contraction time was shortened by 56%. During exercise, the heart rate (fc) increased by 79.4% [from 74.3 (SD 9.3) beats.min-1 to 133.3 (SD 14.8) beats.min-1], and the peak blood velocity (S1) in the common carotid artery increased by 56.1% [from 0.82 (SD 0.10) m.s-1 to 1.28 (SD 0.11) m.s-1]. After exercise, the S1 decreased rapidly to the resting level. The fc decreased more slowly, still being higher than the initial resting level 5 min after exercise. The diastolic velocity wave and the end-diastolic foot decreased during exercise. The blood flow rate in the carotid artery increased transiently by 13.5% at the beginning of exercise [from 5.62 (SD 0.63) ml.s-1 to 6.38 (SD 0.85) ml.s-1] and by 26.5% at the end of the exercise period [from 5.62 (SD 0.63) ml.s-1 to 7.11 (SD 1.34) ml.s-1].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Leukotriene B4 omega-hydroxylase activity in polymorphonuclear leukocytes from patients with inflammatory bowel disease.

omega-oxidation is regarded as the major pathway for the catabolism of leukotriene B4 (LTB4). To determine how LTB4 omega-hydroxylase is modulated in inflammatory bowel disease, we investigated the kinetic characteristics of this enzyme in 10 patients with Crohn's disease (CD), nine with ulcerative colitis (UC) and eight healthy control subjects. After incubating polymorphonuclear leukocytes with various concentrations of 3H-labeled LTB4, omega-oxidation products were separated by high performance liquid chromatography (HPLC) and the radioactivity was measured by a liquid scintillation counter. The apparent Vmax values were significantly higher in both disease than in healthy control subjects, although the difference between CD and UC was insignificant. There was no difference in the apparent Km values. And the Vmax/Km ratios of patients with CD were significantly higher than that of healthy control subjects. It is suggested that LTB4 metabolism is activated in inflammatory bowel disease (IBD) and that the modulation of this enzyme activity has an important role in the pathogenesis of inflammatory bowel disease.

Adolescent↗

PubMed1992

Growth of human cultured cells exposed to a non-homogeneous static magnetic field generated by Sm-Co magnets.

A static magnetic field, with a strong spatial gradient, was established on the surface of cell culture dishes by use of a gilded iron needle set vertically above an Sm-Co magnet. The calculated magnetic flux density was more than 1.5 T at the center of the needle tip, and the products of the flux density and its gradient were about 200 and 60 T2/m at distances of 0.1 and 0.3 mm, respectively, from the center. The DNA content, DNA synthesis and labeling index of cultured cells located within 0.1 mm from the center of the needle, and the growth rate of cells located within 0.3 mm from the center, were measured. HeLa cells grew at a normal rate for 96 h in the magnetic field and showed no significant change in shape, detectable by scanning electron microscopy. The growth of HeLa cells was not influenced by exposure to the magnetic field. Similarly, exposure for 48 h to the magnetic field had no effect on growth of normal human gingival fibroblasts (Gin-1). The DNA content, assayed by microfluorometry of the nuclei of both types of cells stained by the Feulgen reaction, was not significantly different from that of controls. Moreover, exposure to the magnetic field had no effect on DNA synthesis or the labeling index of HeLa cells assayed by autoradiography of incorporated [3H]thymidine. It is concluded that a non-homogeneous magnetic field of the intensity and the gradient used in this study does not significantly influence the growth of HeLa cells or Gin-1 cells.

Cells, Cultured↗