[Tracheal smooth muscle dilation effect by anticholinergic agent in chronic pulmonary emphysema].
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Aged↗
Biomedical subjects
M Sano
Publications and source records attributed to M Sano.
Effect of a new dual neurokinin antagonist on airway smooth muscle in situ.
The effect of FK224 (N-(N2-[N-¿N-(N-2,3-didehydro-N-methyl-N-[N-3- (2-pentylphenyl)-propionyl¿-L-threonyl]tyrosyl-L-leucynyl)-D -phenylalanyl¿-L-allothreonyl]-L-asparaginyl)-L-serine-v-lacto ne, CAS 125787-94-2) on isometric contraction of canine tracheal smooth muscle in situ was studied. Contraction was induced by administration of substance P, neurokinin A, and neurokinin B intra-arterially into the tracheal circulation in five mongrel dogs. FK224 inhibited substance P- and neurokinin A-induced contraction in a dose-dependent manner, but it did not inhibit neurokinin B-induced contraction significantly. These data suggest that FK224 is a dual antagonist of both neurokinin 1 and neurokinin 2 receptors, with a similar potency in in vivo experiments.
Animals↗
Local sprouting of neurites from cultured PC12D cells in response to a concentration gradient of nerve growth factor.
PC12D cells, a subline of PC12 cells, extend neurites very rapidly in response to NGF, even when RNA synthesis is blocked. Several minutes after the initiation of a concentration gradient of NGF from a micropipette in the vicinity of PC12D cells, clear projections emerged from cells on the side facing the micropipette while no significant changes in morphology were observed on the other side of cells. A control solution administered from a micropipette did not produce any changes in morphology. Longer exposure to the gradient of NGF of aggregates of PC12D cells increased the length of neurites extending toward the source of NGF. The observations indicate that the sprouting of neurites occurs locally in regions of PC12D cells that are exposed to an elevated concentration of NGF.
Animals↗
Duration dependent induction of invasive prostatic carcinomas with pharmacological dose of testosterone propionate in rats pretreated with 3,2'-dimethyl-4-aminobiphenyl and development of androgen-independent carcinomas after castration.
Male F344 rats were first treated with 3,2'-dimethyl-4-aminobiphenyl for 20 weeks in the presence of testicular androgens and then administered of a pharmacological dose of testosterone propionate (TP) for various periods (maximum 40 weeks). This resulted in development of invasive carcinomas in the dorso-lateral prostate as well as the seminal vesicles whose incidences were TP duration-dependent. However, in situ carcinomas of the ventral prostate were not affected by the TP treatment and atypical hyperplasias were clearly decreased. When animals were subjected to orchiectomy after 20-weeks-treatment with the TP, invasive adenocarcinomas were still subsequently noted in the dorso-lateral prostate and seminal vesicles, demonstrating a certain androgen-independence. The data indicate that, in spite of the necessity of high dose of TP for induction of invasive prostate carcinomas in the present experimental model, a proportion of the resulting tumors are hormone-independent.
Aminobiphenyl Compounds↗
Staurosporine induces the outgrowth of neurites from the dorsal root ganglion of the chick embryo and PC12D cells.
Staurosporine, a potent inhibitor of protein kinases, caused the rapid outgrowth of neurites from cultured dorsal root ganglia of chick embryos and from PC12D cells, a subline of PC12 cells. Treatment of dorsal root ganglia with 1 to 20 nM staurosporine resulted in the extensive outgrowth of neurites that were indistinguishable from those induced by NGF, as assessed by phase-contrast microscopy, electron microscopy and cytochemical staining of actin and tubulin. However, neurites generated from the ganglia in response to the higher concentrations of staurosporine (40-100 nM) seemed to have different characteristics, possibly as a result of the inhibition of cell migration from ganglia. The sequential changes in morphology of PC12D cells in response to staurosporine and to NGF were revealed by staining of actin. Ruffling membranes emerged at the margins of PC12D cells within 4 min after the addition of staurosporine or of NGF. From 10 min to 24 h after the addition of either compound, the ruffles were transformed into several projections that became growing neurites. The formation of ruffles and the outgrowth of neurites were both apparent at a concentration of staurosporine of 10 nM. The neurites that emerged from PC12D cells in response to staurosporine and in response to NGF were indistinguishable under the phase-contrast microscope and after staining of actin and tubulin. However, staurosporine never promoted survival of PC12D cells in serum-free conditions as that promoted by NGF. The observations indicate that staurosporine at nanomolar concentrations may reproduce the neurogenic changes that induced by NGF in primed neuronal cells, although it can not mimic the action of NGF that supports survival of neurons.
Alkaloids↗
Muscle histopathology in myotonic dystrophy in relation to age and muscular weakness.
We studied histopathological changes in the biceps brachii muscle in relation to age and the degree of muscle weakness in 64 patients (aged 11-59 years) with myotonic dystrophy. The proportion of type 1 fibers was unaltered in the adolescent patients compared with control values, but increased with age. The average diameters of all the fiber types were smaller than control values in the adolescents, suggesting immature development; however, there was an increase in diameter with age that was associated with an increase of hypertrophic type 2 fibers. At all ages, type 1 fibers were smaller than type 2 ones. Small angular fibers and small group atrophy consisted mainly of type 1 fibers, their incidences decreasing with age. The severity of muscular weakness was related to the predominance of type 1 fibers, the reduction in the number of hypertrophic type 2 fibers, and the accumulation of adipose cells, but not to the presence of small angular fibers or to small group atrophy.
Adult↗
Ultrasound bone densitometry of the os calcis in Japanese women.
The velocity (SOS), attenuation slope (BUA) and stiffness index in the os calcis were measured using the 'Achilles' ultrasound bone densitometer (Lunar, Madison, WI). We evaluated the basic attributes of this ultrasound bone densitometer, and showed the age-related changes in ultrasound values in normal Japanese women. The precision was measured in vivo on ten occasions over a 2-week period in 5 subjects. The short-term precision errors (CVs) in vivo were 0.6% for stiffness index, 0.3% for SOS and 1.0% for BUA. Spine, femur neck and total body BMD using dual X-ray absorptiometry (DXA) were highly correlated with stiffness index (r = 0.80, 0.77 and 0.78, respectively) in 194 subjects. Ultrasound values for patients with osteoporosis were significantly lower than those for the normal controls. The Z-score compared with young normals was significantly higher for spine bone mineral density (-4.4) than for stiffness index (-3.5); BUA and SOS gave significantly lower Z-scores -2.9 and -3.0, respectively). Ultrasound values were also lower compared with age-matched normal controls. The Z-score for stiffness index (-2.1) was significantly superior to that for either SOS or BUA (-1.5). Age-related change in ultrasound values was evaluated in 842 normal women. There was a decline in stiffness index of about 24% from the values in young adulthood to those of women in their seventies, about 75% of which occurred from age 44-49 years onward. These findings seem to indicate that the menopause affected the change in ultrasound values.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Urinary excretion of pyridinium crosslinks of collagen in oophorectomized women as markers for bone resorption.
To detect increased bone resorption in estrogen-deficient women, the urinary excretion of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), which are intermolecular crosslinkings of collagen fibers, were measured and their chronological changes were evaluated following oophorectomy. Seventy-five women were divided into three groups; 15 premenopausal women (mean age 44.0 years), 15 postmenopausal women (mean age 54.2 years) and 45 surgically menopausal women who had a normal menstrual cycle before surgery (mean age 42.2 years). There was a significant increase in HP and LP of the postmenopausal women (P < 0.001). In the oophorectomized women, both HP and LP were three times higher than those of premenopausal women within 1 year after oophorectomy, and decreased to the same level of the postmenopause between 2 and 3 years after surgery. In the six oophorectomized women after the administration of estrogen, HP and LP both decreased remarkably in all cases. The present study thus indicates that an increase of bone resorption which was evaluated by urinary HP and LP occurs in the early stage after oophorectomy. It may, therefore, be good to begin estrogen replacement therapy as soon as possible after oophorectomy.
Adult↗
Elevation of the phospholipase A2 activity in peritoneal fluid cells from women with endometriosis.
OBJECTIVE: To assess the prostaglandin (PG) production on peritoneal fluid (PF) cells, phospholipase A2 (PLA2) activity of those cells in women with endometriosis was measured and compared with that of women without endometriosis. DESIGN: Prospective clinical controlled study. PATIENTS: Women who underwent laparoscopy and were found either to have endometriosis (n = 15) or not (n = 9) were included in this study. Mononuclear cells obtained from the patients at laparoscopy were immediately separated by a Ficoll-Paque technique, lysed by nitrogen cavitation, and stored at -80 degrees C. INTERVENTIONS: Phospholipase A2 activity was measured by Dole assay using 1-palmitoyl-2-[1-14C] palmitoyl phosphatidyl choline and assessed on a protein basis and a cell number basis. RESULTS: There were at least four measurable kinds of PLA2 activity detected in the cells: two calcium-dependent pH optima 7.0 and 9.0 activities and two calcium-independent pH optima 7.5 and 8.5 activities. A calcium-dependent and pH optima 9.0 activity was the highest, and it was significantly higher in women with endometriosis when compared with those who did not have endometriosis. CONCLUSION: These results indicate that the increase in the PGs in PF with endometriosis may be produced by PF cells in which PLA2 activity is elevated.
Adult↗
Urinary pyridinoline and deoxypyridinoline in prostate carcinoma patients with bone metastasis.
Bone metastases from prostate carcinoma are predominantly osteoblastic. Recently, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been employed as indicators of bone resorption. In this study, we evaluated urinary Pyr and Dpyr levels in 19 prostate carcinoma patients, of whom 12 had bone metastasis and seven had not, and 11 age-matched control subjects. There was a significant difference in Pyr levels between the control group and the patients with metastasis (mean +/- s.d., 19.5 +/- 7.2 vs 73.3 +/- 67.1 nmol mmol-1 creatinine, P < 0.05). The mean level of Dpyr in the patients with metastasis (10.8 +/- 8.0 nmol mmol-1 creatinine) was significantly higher than that in the control group (3.1 +/- 2.1 nmol mmol-1 creatinine, P < 0.01), and also higher than that in the patients without metastasis (3.5 +/- 1.9 nmol mmol-1 creatinine, P < 0.05). There was no significant difference in Pyr and Dpyr levels between the control group and the patients without metastasis. These results suggest that bone resorption is also accelerated in prostate carcinoma patients with bone metastasis.
Aged↗
Potentiation of oxidative damage to rat red blood cells by the concurrent presence of t-butyl hydroperoxide and bromotrichloromethane.
Recently potentiation of oxidative damage in rat red blood cells (rRBC) incubated with t-butylhydroperoxide (BHP) in combination with bromotrichloromethane (BrCCI3) was demonstrated. The mechanism by which this combination (BrCCI3/BHP) potentiates the oxidative damage to rRBC was investigated in this study. When rRBC were incubated with 0.1 mM BHP, 0.5 mM BrCCI3, or the two combined, BrCCI3/BHP-potentiated lipid peroxidation and hemolysis were further enhanced under anaerobic conditions. However, the potentiation of lipid peroxidation was abolished by heating or trypsin digestion of rRBC. Electron spin resonance (ESR) studies demonstrated an increase of alkoyl radical induced by BrCCI3/BHP in rRBC, and this increase was abolished by heating or predigestion of hemolysates with trypsin. The inhibition of lipid peroxidation by diphenylamine (which reacts with alkoxyl radicals but not peroxyl radicals) suggests an important role of alkoxyl radicals. Overall, the present findings demonstrate that the increase in radical-related oxidative damage, possibly mediated by proteinlike materials, may be at least partially responsible for the potentiation of damage to rRBC induced by BrCCI3/BHP, and perhaps by BrCCI3. Although the in vivo significance of these results remains to be investigated, it seems likely that halocarbon toxicity may be amplified by elevated levels of lipid peroxide in blood.
Animals↗
Assessing patient dependence in Alzheimer's disease.
BACKGROUND: While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. METHODS: In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS > or = 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. RESULTS: The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. CONCLUSION: Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD.
Activities of Daily Living↗
Cytotoxic cells directed against placental cells detected in human habitual abortions by an in vitro terminal labeling assay.
PROBLEM: From the clinical point of view, it has been proposed that an immunological imbalance between the mother and the fetus might exist in one of the mechanisms for human habitual abortion. However, in the definition of habitual abortion, we have no distinct immunological criteria for this clinical entity at the moment. METHOD: We employed aborted placental cells as the target cells in an in vitro terminal labeling (IVTL) assay system, in which the cytotoxic activity of maternal peripheral blood mononuclear cells (PBMCs) against the placental cell was examined. RESULTS: Our results showed that the cytotoxic activity of maternal PBMCs was significantly higher in the habitual aborters (the mean target cell destruction: %TCD = 34.9%, N = 14) than that in the women with a normal first trimester (the mean % TCD = 8.9%, N = 14, P < .01). The results from the IVTL assay did not correlate with other assays using paternal lymphocytes as the target cells. The surface marker analyses revealed that CD16+ cells, CD14+ cells, and CD5+ cells were involved in the cytotoxic response against the placental cells in various degrees among the cases. CONCLUSIONS: The above evidence suggests that a variety of cytotoxic cells participate in the phenomenon of human habitual abortion.
Abortion, Habitual↗
[Inhibition of biofilm formation by clarithromycin (CAM) in an experimental model of complicated bladder infection--in vitro study using automated simulation of urinary antimicrobial concentration].
The role of clarithromycin (CAM) in biofilm formation has recently been reported. Inhibition of the production or promotion of the dissolution of the glycocalyx, a major component of biofilm, has been implicated in its mechanism of action. However, the details remain unclear. We used an experimental model of complicated urinary bladder infection and automated simulation of the variations in urinary antimicrobial concentration to study the efficacy of CMA in inhibiting biofilm formation and obtained the following results. 1) Prior to biofilm formation, Pseudomonas aeruginosa (P. aeruginosa) was exposed to ciprofloxacin (CPFX, MIC: 8 micrograms/ml), which was active against the organism, at a dose of 200 mg t.i.d. for 7 days. The bacteria were apparently eradicated from the culture medium in the experimental model of bladder infection (model bladder) after 32 hours. However, when the medium was changed to eliminate the antimicrobial agent on Day 7, bacterial regrowth was initiated after 4 hours. Scanning electron microscopy demonstrated sequential biofilm formation on the surface of glass beads in the model bladder diverticulumn, suggesting inside the biofilm were a source of regrowth. 2) Prior to biofilm formation, P. aeruginosa was also exposed to CAM alone, which has no antimicrobial activity against the organism (MIC: > 128 micrograms/ml) at a dose of 200 mg t.i.d. for 7 days. In this situation, CAM was not active against P. aeruginosa and the bactericidal concentration in the model bladder did not decrease markedly, reaching the initial level (10(7) CFU/ml) within 48 hours. However, although numerous bacteria were attached to the glass beads in the diverticulum, no biofilm was formed. 3) Exposure to a combination of CPFX and CAM (each at 200 mg t.i.d. for 7 days) resulted in the eradication of bacteria from the model bladder at 32 hours, and no bacterial regrowth was demonstrated after the medium was exchanged on Day 7. In addition, no biofilm was formed and the bacteria did not become attached to the glass beads. 4) The content of alginate, a major component of P. aeruginosa biofilm, was measured per 5 glass beads on Day 3, 5, and 7 after starting drug administration. The alginate content increased with time when CPFX was given alone at a dose of 200 mg t.i.d..(ABSTRACT TRUNCATED AT 400 WORDS)
Biofilms↗
[Study on MIC breakpoint and method of antimicrobial chemotherapy for moderately complicated urinary tract infection--study using an automatic simulator of urinary antimicrobial agent concentrations].
We experimentally investigated an efficient administrating method of antimicribials prior to the clinical treatment of complicated urinary tract infection without catheter. An experimental model of moderately complicated urinary tract infection, which can simulate changes in the urinary concentration of antimicrobials by means of previously reported computer control method, was used for the experiment. The following results were obtained. 1. At first, for complicated UTI cases without an indwelling catheter, an investigation was made of the clinical therapy results to determine the upper MIC range of bacteria, including isolated strains, that can be nearly eliminated following treatment, by the administration method. We then estimated the clinical breakpoint. 2. By adjusting the size of the diverticulum in a urinary bladder model, we prepared a model which gave comparatively good agreement between the clinical and experimental breakpoints. 3. The clinical therapy results revealed that by the clinical breakpoint was higher in degree of coverage of the MIC distribution of causative bacteria associated with a higher actual clinical elimination rate and a higher efficacy rate. 4. It was surmised that an efficient administration method for complicated UTI without an indwelling catheter can be established if the urinary bladder model and the following approach are applied: prior to clinical treatment it should be determined what would be high enough to cover 70% of the MIC distribution of the estimated causative bacteria of UTI, and then an administration method which would yield that concentration as the experimental breakpoint should be devised.
Anti-Bacterial Agents↗
[Therapeutic study on biofilm of the urinary tract using a severely complicated bladder model (biofilm model of the urinary tract)--experimental study using an automatic simulator of urinary antimicrobial agent concentration, and clinical study].
For the purpose of conducting a therapeutic study on biofilm of the urinary tract, we devised a computer-controlled severely complicated bladder model (biofilm model of the urinary tract) enabling us to simulate the time-course of the concentration of antimicrobial agents in the urine. Using this model, we investigated clarithromycin (CAM), which has been reported to have anti-biofilm action, at concentrations close to its urinary levels at the time of clinical use in order to predict its effect on biofilm of the urinary tract. On the basis of those experimental results, we also conducted a clinical examination. The following results were obtained. 1. The action of ciprofloxacin (CPFX, MIC: 8 micrograms/ml) alone, which shows anti-P. aeruginosa activity, caused apparent elimination of P. aeruginosa from the model. However, regrowth of the microbes occurred when CPFX was removed from the bladder model. Moreover, the biofilm was not eliminated by the antimicrobial action of CPFX, and this was surmised to be the cause of the regrowth. 2. CAM (MIC: above 128 micrograms/ml), which has no anti-P. aeruginosa activity, was similarly tested as anti-biofilm agent when added alone to the biofilm model. The P. aeruginosa recovered to its initial concentration within 48 hours, but the biofilm disappeared due to the action of CAM. 3. The combined action of CPFX and CAM caused microbial elimination from the bladder model without microbial regrowth, even after these antimicrobial agents were removed from the bladder model. After the action of CPFX and CAM, the biofilm disappeared, and no microbial adherence was noted. 4. Measurement of time-course of the alginate content, which is the main component of P. aeruginosa biofilm, in the presence of CAM found that the alginate content decreased below the limit of detection after day 5. 5. The clinical study of complicated urinary tract infection revealed the microbial elimination rate and the efficacy rate to be higher in the combined CPFX-CAM administration group than in the CPFX-only administration group. 6. Based on the above results, we surmise that the combined use of an antimicrobial agent which is active against the causative microbe and anti-biofilm agent such as CAM will show some degree of efficacy in eliminating biofilm of the urinary tract.
Ciprofloxacin↗
[Adaptation study for biofilm of the urinary tract via highly complicated bladder model (biofilm model of the urinary tract)--experimental study using automatic simulator of the urinary antimicrobial agent concentration].
With the view of making an adaptation study for biofilm of the urinary tract, we devised a computer-controlled highly complicated bladder model (biofilm model of the urinary tract) that allowed the simulation of time-course changes in the urinary concentration of antimicrobial agents. Clarithromycin (CAM), which is reported to have an anti-biofilm action, was examined at urinary levels approximating clinical concentrations and its effect on biofilm was determined. The following results were obtained. 1) Ofloxacin (OFLX, 200 mg x 2/day, MIC; 8 micrograms/ml), which is active against Pseudomonas aruginosa, caused apparent microbial elimination from the model at 42 hours, but bacterial regrowth occurred 4 hours after withdrawal of this agent. No disappearance of the biofilm was noted with OFLX suggesting that this was the cause of bacterial regrowth. 2) The combination of OFLX (200 mg x 2/day) and CAM (MIC; > 128 micrograms/ml, 200 mg x 2/day) on anti-biofilm agent, with no effect on P. aeruginosa, eliminated bacteria from the bladder model more rapidly and prolonged the regrowth time to 10 hours after withdrawal of the antimicrobial agents. Disappearance of most of the biofilm and only slight microbial adhesion was noted. 3) The combination of OFLX (200 mg x 2/day) and CAM (400 mg x 3/day) caused microbial elimination from the bladder model with no regrowth at 30 hours after withdrawal of the antimicrobial agents. The biofilm disappeared completely and no microbial adhesion was noted. 4) CAM alone (400 mg x 3/day) allowed microbial recovery to the initial level within 48 hours after withdrawal, but led to disappearance of the biofilm and the adhesion of microbes without a glycocalyx. 5) These results suggest that the anti-biofilm action of CAM is dose-dependent, and that combined use of an appropriate antimicrobial agent and anti-biofilm agent like CAM may be effective for biofilm infections of the urinary tract.
Anti-Bacterial Agents↗
Purification and some properties of alpha-L-arabinofuranosidase from Bacillus subtilis 3-6.
alpha-L-Arabinofuranosidase (EC 3.2.1.55) was purified from culture supernatant of Bacillus subtilis 3-6. The enzyme had a molecular weight of 61,000 and displayed maximum activity at pH 7.0 and 60 degrees C. It released arabinose from O-alpha-L-arabinofuranosyl-(1-->3)-O-beta-D-xylopyranosyl-(1-->4)-D-x ylopyranos e (A1X2), O-beta-D-xylopyranosyl-(1-->4)-[O-alpha-L-arabinofuranosyl-(1-->3)]- O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (A1X3), and arabinan, but not from O-beta-D-xylopyranosyl-(1-->2)-O-alpha-L- arabinofuranosyl-(1-->3)-O-beta-D-xylopyranosyl-(1-->4)-O-beta-D-xylopyr anosyl- (1-->4)-D-xylopyranose (A1X4), arabinoxylan, gum arabic, or arabinogalactan.
Amino Acid Sequence↗