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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 199 records · Page 11Linked to original sources
PubMed1997

Potent NK1 receptor antagonists: synthesis and antagonistic activity of various heterocycles with an N-[3,5-bis(trifluoromethyl)benzyl]-N-methylcarbamoyl substituent.

Various N-[3,5-bis(trifluoromethyl)benzyl]-N-methylcarbamoyl heterocycles (1, 2 and 3) modified at rings A and B in the isoquinolone (1a) and pyrido[3,4-b]pyridine (2a) nuclei were prepared and evaluated for NK1 receptor antagonistic activities. The structure-activity relationship studies on this series, along with conformational analysis, showed that (i) for ring A, 6-membered heterocycles are preferable to 5-membered heterocycles (a ca. 300-fold difference in potency), (ii) the 6-membered ring seems to function as an anchor by fixing the pendant phenyl group in a desirable orientation for receptor binding, and (iii) since compounds with aromatic rings (2) and those with aliphatic rings (3) as ring B both show good potency, this ring does not seem to be essential for receptor recognition. Among the compounds synthesized, the tetrahydropyridine derivatives 3a, 3b and 3f exhibited excellent inhibitory effects both in vitro and in vivo, with potent activity upon oral administration (ED50 = 0.20-0.27 mg/kg) (capsaicin-induced plasma extravasation in guinea pig trachea).

Administration, Oral↗
PubMed1997

The effects of class I drugs on the cycle length of sustained ventricular tachycardia and the signal-averaged electrocardiogram.

Evaluation of signal-averaged electrocardiograms (SAECGs) has been reported to be useful for predicting the patients with sustained ventricular tachycardia (SVT) combined with organic heart disease and at high risk for sudden cardiac death. However, the relationship between drug efficacy and SAECGs has not been established. We studied the effects of class I drugs on SVT using SAECGs. The study group consisted of 13 patients with SVT who underwent serial electropharmacologic trials. In 7 trials, SVT could not be induced after administration of class I drugs (group 1). In 17 trials, SVT was still inducible (group 2). Filtered QRS in group 2 were significantly prolonged after administration of class I drugs (p < 0.05). The prolongation of the SVT cycle length was correlated with the prolongation of the original QRS (p < 0.05) and with prolongation of the filtered QRS after administration of class I drugs (p < 0.01). The evaluation of the effects of class I drugs on SAECGs may be useful in predicting the inducibility of SVT and SVT cycle length.

Aged↗
PubMed1997

Negative charges bound to collagen fibrils in the rabbit articular cartilage: a light and electron microscopic study using cationic colloidal iron.

Negative charged sites in the normal rabbit articular cartilage were investigated using cationic colloidal iron methods. In light microscopy of the cartilage stained with the colloidal iron at pH 1.5, a distinct Prussian blue reaction was observed in the pericellular matrix, and a weak blue reaction in the territorial and interterritorial matrices. At pH 7.0, a diffuse Prussian blue reaction was observed in the pericellular and interterritorial matrices. Digestion with chondroitinase ABC, hyaluronidase and keratanase could not erase the Prussian blue reaction. However, the sections digested with collagenase followed by chondroitinase ABC showed significant elimination of the Prussian blue reaction. Electron microscopy of ultrathin sections stained with the colloidal iron at pH 1.5 revealed that the cationic colloid particles were deposited abundantly in the pericellular matrix and dotted along collagen fibrils in the territorial and interterritorial matrices. The present results suggest that negatively charged sites in the articular cartilage derive mostly from chondroitin sulfate, whose proteoglycans firmly bind to collagen fibrils. Such an ultrastructure may maintain the electrostatic microenvironment in the collagen plexus, holding much water in the cartilage matrix, and also producing biomechanical properties such as tensile strength and elasticity of the cartilage.

Animals↗
PubMed1997

Effect of repeated exercise on urinary 8-hydroxy-deoxyguanosine excretion in humans.

The purpose of this study was to investigate the effect of repeated exercise on oxidative damage to DNA in 10 well trained long distance runners who participated in an 8-day training camp. The average running distance during the camp was 30 +/- 3 km/day. The amount of urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion was used to estimate the oxidative DNA damage. Urine samples were collected for both a 3-day control period as well as throughout the camp. Blood samples were drawn after overnight fasting both before and after the camp. Urinary 8-OHdG excretion was significantly increased during the camp compared to the control period (265.7 +/- 75.5 vs. 335.6 +/- 107.4 pmol/kg/day, P < 0.05). The content of 8-OHdG in the lymphocyte DNA on the day after finishing the camp did not differ from that before the camp. Plasma TBARS, LDH, CK, CK-MB, and myoglobin significantly rose after the camp (P < 0.05). The plasma beta-carotene levels tended to rise after the camp, while the plasma alpha-tocopherol levels increased significantly after the camp (P < 0.05). These results indicate that repeated exercise augments oxidative stress and the DNA is also injured by exercise-induced reactive oxygen species. However, the oxidative damage to DNA is not accumulated by consecutive exercise, although it is sustained as long as the exercise is repeated.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Effect of endurance exercise on the tissue 8-hydroxy-deoxyguanosine content in dogs.

The purpose of this study was to investigate the effect of endurance exercise on both the tissue and lymphocyte 8-hydroxy-deoxyguanosine (8-OHdG) content. Six dogs ran on a treadmill for 7 hours. Another six dogs were assigned to a sedentary control group. The exercised dogs were sacrificed immediately after exercise and the counterpart of the sedentary group was also sacrificed at the same time. The brain, lung, liver, spleen, kidney, jejunum, colon, diaphragm, heart, splenius muscle, and the medial and lateral portion of gastrocnemius muscle samples were then collected. Lymphocytes were sampled before and after exercise in the exercised dogs. The 8-OHdG content of lymphocyte DNA was found to significantly decrease after exercise (0.57 +/- 0.19 vs 0.33 +/- 0.10/deoxyguanosine (dG) x 10(5), P < 0.05). The colon was the only tissue which showed a significant decrease in the content (0.83 +/- 0.24 vs 0.54 +/- 0.15/dG x 10(5), P < 0.05). No tissue except for the colon showed any significant changes after exercise. These results therefore indicate that, immediately after endurance exercise, an augmented repair mechanism might thus play a role in the decrease of 8-OHdG in the lymphocytes and the colon, while the 8-OHdG generation might be counterbalanced by its repair in other tissues.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Effect of a single bout of exercise and beta-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans.

We investigated the effects of acute exhaustive exercise and beta-carotene supplementation on urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion in healthy nonsmoking men. Fourteen untrained male (19-22 years old) volunteers participated in a double blind design. The subjects were randomly assigned to either the beta-carotene or placebo supplement group. Eight subjects were given 30 mg of beta-carotene per day for 1 month, while six subjects were given a placebo for the same period. All subjects performed incremental exercise to exhaustion on a bicycle ergometer both before and after the 1-month beta-carotene supplementation period. The blood lactate and pyruvate concentrations significantly increased immediately after exercise in both groups. The baseline plasma beta-carotene concentration was significantly 17-fold higher after beta-carotene supplementation. The plasma beta-carotene decreased immediately after both trials of exercise, suggesting that beta-carotene may contribute to the protection of the increasing oxidative stress during exercise. Both plasma hypoxanthine and xanthine increased immediately after exercise before and after supplementation. This thus suggests that both trials of exercise might enhance the oxidative stress. The 24-h urinary excretion of 8-OHdG was unchanged for 3 days after exercise before and after supplementation in both groups. However, the baseline urinary excretion of 8-OHdG before exercise tended to be lower after beta-carotene supplementation. These results thus suggest that a single bout of incremental exercise does not induce the oxidative DNA damage, while beta-carotene supplementation may attenuate it.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

[Reliability and validity of a self-administered questionnaire of patient health care behavior and satisfaction].

The reliability of a self-administered questionnaire of health care behavior and patient satisfaction, and also the validity of measuring patient satisfaction by a single question, were investigated on 754 outpatients and 204 inpatients. In order to assess the reliability and the validity, the questionnaire was administrated twice. Subjects for reliability tests were 194 outpatients and 91 inpatients and validity tests were performed with 280 outpatients and 84 inpatients. To assess the validity of patient satisfaction, supplementary questions about satisfaction (outpatients 22 items, inpatients 14 items) were included in the questionnaire. Reliability was assessed using kappa coefficient and proportion of agreement. To assess validity, principal component analysis was performed, and the correlation between principal-components and the score of patient satisfaction was analyzed. With the exception of patient understanding of the doctor's explanation and patient satisfaction, kappa coefficient and proportion of agreement were high (kappa: 0.4 approximately 0.82), indicating that question contents were objective and easily understood. By making the question categories simple, a higher kappa coefficient and proportion of agreement in patient understanding about doctor's explanation and patient satisfaction were achieved. This suggests that in questionnaire, similar question category must be made simple or similar categories should be put together in analysis. Spearman's correlation coefficient between the question about patient satisfaction and the first principal component (which summarizes all of the questions about patient satisfaction) was high (outpatients: 0.63, inpatients: 0.67). Therefore the validity of measuring general information about patient satisfaction by using a single question is suggested.

Female↗
PubMed1997

[Clinical statistics on in-patients and operations during a 20-year period (1975-1994) at Department of Urology, Kansai Medical University].

The patients, diseases and operations experienced between 1975 and 1994 in our department were statistically analyzed. The numbers of in-patients and operations have been increasing since 1977. During these 20 years, endoscopic surgery has replaced many open surgical procedures. The introduction of extracorporeal shock wave lithotripsy has dramatically changed the therapeutic modality for urolithiasis, and decreased of the necessity of open surgery.

Female↗
PubMed1997

[Idiopathic interstitial pneumonia associated with a high level of CA19-9 in serum and with CA19-9 in lung tissue].

A 65-year-old man was admitted to our hospital because of mild dyspnea. A chest roentgenogram showed diffuse reticulonodular shadows in both lung fields. The concentration of CA19-9 in serum was high. Pancreatic cancer and other diseases were considered as causes, but no definitive diagnosis could be made. An open-lung biopsy was done, and examination of a specimen resulted in the diagnosis of idiopathic interstitial pneumonia (chronic type). Immunohistochemical staining with anti-CA19-9 antibody was positive. The lumens of microscopic honeycomb structures and fibrotic areas were covered with flattened and cuboidal metaplastic epithelial cells, which stained positively for anti-CA19-9 antibody.

Aged↗
PubMed1997

Novel elements located at -504 to -399 bp of the promoter region regulated the expression of the human macrophage scavenger receptor gene in murine macrophages.

The expressions of type I and type II macrophage scavenger receptors (MSRs) are highly specific in macrophages and related cell types. Although some reports have described the regulation of MSR gene expression and proposed some cis-elements related to cell-specific expression, the regulation of MSR remains largely unclear. This is due, in part, to an unacceptably low efficiency of transfection into monocyte/ macrophage cells. In the present study, we optimized the conditions of electroporation in murine macrophage (P388D1) cells. The efficiency of electroporation was increased 20-fold compared with previous methods. Using the optimized method, we focused on studying the regulation of the human MSR promoter in macrophages. We presently demonstrate that: a) the proximal -10 to +50 bp human MSR promoter region is necessary for the cell type-specific expression of human MSR; b) the 6.5 kbp upstream sequence suppresses the expression of human MSR; c) a promoter region extending from -504 to -399 bp produced the greatest increase in transcriptional activity; d) macrophage cell-specific transcription factors bind to the region as determined by electrophoretic mobility shift assay (EMSA) and a footprint assay; and e) mutations of the region reduced about 40-75% of the promoter activity in a transfecting assay. We concluded that novel elements located at the -504 to -399 bp region may play an important role in the regulation of the MSR gene expression in macrophages. We speculate that macrophage-specific factors binding to those elements may be responsible for the transcription regulation of the MSR gene in macrophages.

Animals↗
PubMed1997

Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)

We report a patient with herpetiform pemphigus (HP) who showed reactivity only with pemphigus vulgaris (PV) antigen but not with pemphigus foliaceus (PF) antigen. Direct and indirect immunofluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid-separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV, in addition to PF, with unique clinical and histological features.

Autoantigens↗
PubMed1997

[Record linkage of the elderly in the national surveys on the geriatric intermediate care facility].

Geriatric intermediate care facility, GICF, have been established since 1986 in Japan. The term of 'intermediate' denotes a facility midpoint between a hospital and home, with a powerful rehabilitation function. The annual governmental survey on GICF has been applied to all GICFs in Japan since 1989. This survey is a cross-sectional-type survey. For evaluating the role of GICF, we considered a type of cohort study using these surveys for four years by means of a record linkage method. This method is possible, because subjects of a survey for any year become subjects in the survey of the following year, if they have been in a GICF for more than one year. In this paper, for the purpose of preparing for a study of the role of GICF, we report some results about a record linkage for these surveys, and two continuing rates were calculated for these cohorts. Sources were personal records in 1989 to 1992 gathered by The National Survey on GICF in Japan. The record linkage method is as follows. We divided the annual personal records into several files by both the periods of the last admission and the survey year. Three cohorts, i.e. a cohort-89, a cohort-90 and a cohort-91 for persons for whom the first survey was 1989, 1990 and 1991, respectively are thus obtained. Next, we identified individuals from the annual files in each cohort. As personal names were not available, we identified individuals by sex, birth date, date of admission and facility number by the use of a personal computer and a FORTRAN program. Results were as follows. 1. Multiple matched persons were few (0.5% or less), and identification rates were 90% or more, despite the fact that basic linking variables were used. 2. Continuing rates were about 40% and decreased with new cohorts, while those of a fixed cohort were increased as length of stay increased. These reveal that recent admissions who stay continuously at a GICF were decreasing, but the longer the period for which the elderly stays at a GICF, the less possibility that he will be discharged. 3. Between record agreement rates for individuals over two years for unchangeable characteristics such as a place before admission which are expected to be 100% were about 80%. 4. A record linkage method appears to be useful for calculating continuing rates classified by any attribute.

Aged↗
PubMed1997

[Clinical efficacy of post-TUR prophylactic chemotherapy for superficial bladder cancer--the result of co-operative prospective randomized trial].

We have performed a prospective randomized clinical trial of post-operative prophylactic therapy for superficial bladder cancer since October in 1991. The criteria were as follows; age < or = 80 y.o., Ta/T1, TCC G1/G2, without CIS lesion and resectable cancer by TUR. The therapeutic arm was divided into three as follows: arm A intracystic instillation with Epirubicin; arm B: oral administration with 5-FU; arm C: combination of arm A and arm B. The number of registered patients were 20 in arm A, 18 in arm B, and 18 in arm C. The patient characteristics in every group were not significantly different. The prophylactic efficacy of arm A was superior to that in the other two groups.

Administration, Intravesical↗
PubMed1997

[Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus].

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.

Antigens, CD↗
PubMed1996

Identification of significant residues in the substrate binding site of Bacillus stearothermophilus farnesyl diphosphate synthase.

Farnesyl diphosphate synthases have been shown to possess seven highly conserved regions (I-VII) in their amino acid sequences [Koyama et al. (1993) J. Biochem. (Tokyo) 113, 355-363]. Site-directed mutants of farnesyl diphosphate synthase from Bacillus stearothermophilus were made to evaluate the roles of the conserved aspartic acids in region VI and lysines in regions I, V, and VI. The aspartate at position 224 was changed to alanine or glutamate (mutants designated as D224A and D224E, respectively); aspartates at positions 225 and 228 were changed to isoleucine and alanine (D225I, D228A); lysine at position 238 was changed to either alanine or arginine (K238A, K238R). The lysines at positions 47 and 183 were changed to isoleucine and alanine (K471, K183A), respectively. Kinetic analyses of the wild-type and mutant enzymes indicated that the mutagenesis of Asp-224 and Asp-225 resulted in a decrease of Kcat values of approximately 10(4)- to 10(5)-fold compared to the wild type. On the other hand, D228A showed a Kcat value approximately one-tenth of that of the wild type, and the k(m) value for isopentenyl diphosphate increased approximately 10-fold. Both K471 and K183A showed k(m) values for isopentenyl diphosphate 20-fold larger and kcat values 70-fold smaller than the wild type. These results suggest that the two conserved lysines in regions I and V contribute to the binding of isopentenyl diphosphate and that the first and the second aspartates in region VI are involved in catalytic function. Aspartate-228 is also important for the binding of isopentenyl diphosphate rather than for catalytic reaction.

Acyclic Monoterpenes↗
PubMed1996

Extracellular K+ and intracellular pH allosterically regulate renal Kir1.1 channels.

The channels that control K+ homeostasis by mediating K+ secretion across the apical membrane of renal tubular cells have recently been cloned and designated ROMK1, -2, and -3. Native apical K+ channels are indirectly regulated by the K+ concentration at the basolateral membrane through a cascade of intracellular second messengers. It is shown here that ROMK1 (Kir1.1) channels are also directly regulated by the extracellular (apical) K+ concentration, and that this K+ regulation is coupled to intracellular pH. The K+ regulation and its coupling to pH were assigned to different structural parts of the channel protein. K+ regulation is determined by the core region, which comprises the two hydrophobic segments M1 and M2 and the P region. Decoupling from pH was achieved by exchanging the N terminus of ROMK1 by that of the pH-insensitive channel IRK1 (Kir2.1). These results suggest an allosteric regulation of ROMK1 channels by extracellular K+ and intracellular pH, which may represent a novel link between K+ homeostasis and pH control.

Allosteric Regulation↗
PubMed1996

High-Spatial-Resolution Medical-Imaging System Using a HARPICON Camera Coupled with a Fluorescent Screen.

A high-sensitivity HARPICON camera was developed for medical X-ray imaging using a fluorescent screen. It is an avalanche-multiplication-type image pick-up tube and is 32 times more sensitive than conventional tubes. The camera also has a wider dynamic range than conventional medical-imaging cameras because a maximum output signal current of 2.3 muA is obtained and, in high-illumination-intensity regions, photocurrent is not proportional to illumination intensity. The fluorescent screen is an intensifying screen of the type used for radiographic screen-film combinations in medical examination. An X-ray image on the screen is focused on the photoconductive layer of the pick-up tube using a coupling lens with f/0.65. Experiments were performed using monochromated X-rays at the Photon Factory. An image of a spatial resolution test chart was taken in a 525 scanning-line mode of the camera. The chart pattern of 5 line-pairs mm(-1 )(spatial resolution of 100 mum) was observed at an X-ray input field of 50 x 50 mm. Real-time digital images of the heart of a 12 kg dog were obtained at a frame rate of 60 images s(-1) after injection of a contrast medium into an artery. The images were stored in digital format at 512 x 480 pixels with 12 bits pixel(-1). High-spatial-resolution and high-contrast images of coronary arteries were obtained in aortography using X-rays with energy above that of the iodine K edge; the image quality was comparable with that of conventional selective coronary angiography.

Journal Article↗