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Biomedical subjects

K Hisamatsu

Publications and source records attributed to K Hisamatsu.

At least 37 records · Page 2Linked to original sources

Detection of specific IgE antibodies to Japanese cypress pollen in patients with nasal allergy: a comparative study with Japanese cedar.

Japanese cypress pollinosis has recently attracted attention and its clinical relationship with Japanese cedar pollinosis has been pointed out. To compare the two kinds of pollinosis, we retrospectively examined specific IgE antibodies to both pollen of Japanese cypress and cedar in the sera of 150 patients with nasal allergy using AlaSTAT assay. During the season in which the pollens of these two species are dispersed, the positive rates for Japanese cypress and cedar increased to 51.4 and 75.0%, respectively. The percentage of patients positive for both of cypress and cedar was elevated to 51.4%, corresponding to 68.5% of the total patient group positive for cedar. Almost all the cases positive for cypress had IgE antibodies to cedar, the value of which was considerably higher than that of cases positive only for cedar. Furthermore, increases in titers of specific IgE antibodies to cypress was observed in four of six cases, compared between specific IgE antibodies to cypress in pre- and post-dispersion of cypress pollen. These findings suggest the following possibility: (i) there is cross-antigenicity between the two pollen species, and (ii) patients are immunologically affected by cypress pollen to express higher levels of specific IgE antibodies after pollen dispersion.

Adolescent↗

Eosinophil cationic protein in perennial allergic rhinitis.

For a quantitative investigation of eosinophil activation in perennial allergic rhinitis, eosinophil cationic protein (ECP) concentrations were measured by a radioimmunoassay in serum, nasal secretions (ECPWN) and in the supernatant of these nasal secretions (ECPsup) obtained from normal subjects and allergic patients. Levels of ECPWN and ECPsup were higher than that of ECPserum. ECPsup showed a positive correlation with clinical severity, despite the lack of a significant correlation with eosinophilia in nasal smears. ECPWN and ECPserum showed no significant correlation with any of these clinical parameters. There was a weak tendency toward an increase in histamine sensitivity of the nasal mucosa of allergic patients with higher ECPsup although this was not statistically significant. These results suggest accumulation and activation of eosinophils in the allergic nasal mucosa, and also indicate that ECPsup may be a clinical parameter of perennial allergic rhinitis.

Blood Proteins↗

[Isolation of alpha-streptococci with inhibitory activity against pathogens, in the oral cavity and the effect of tobacco and gargling on oral flora].

We investigated the distribution of oral alpha-streptococci with inhibitory activity against pathogens, which compose an oral defense mechanism. Detection rate of alpha-streptococci with inhibitory activity against S. pyogenes and S. aureus derived from the tonsil was higher than in other portions, the tongue, cheek, gingiva, or saliva. It has suggested that tonsillar bacterial flora are mainly a defense mechanism. The oral flora in healthy smokers was compared with healthy non-smokers to investigate the influence of tobacco on oral bacterial flora. The results showed that the detection rate of S. aureus in smokers was higher while that of alpha-streptococci with inhibitory activity against S. aureus was lower. However, the detection rate of alpha-streptococci with inhibitory activity against S. pyogenes in smokers was as high as in non-smokers. It is suggested that it was easy for S. aureus to adhere to the oral mucosa in smokers, and was considered to influence the strain which produces beta-lactamase for medical treatment. We investigated the influence of gargling on oral bacterial flora by comparing the amount of bacteria before and after gargling with popidine-iodine gargle and saline solution. It was shown that alpha-streptococci, a main component of normal oral flora were decreased after gargling in both smokers and non-smokers. Furthermore, it was shown that group A Streptococcus was not decreased after gargling, and it was concluded that use of gargle medicinal mouth wash in bacillus carriers should be studied further.

Adult↗

[Participation in causing O.M.E. with nasopharyngeal alpha-Streptococcus].

The role of normal pharyngeal flora in the defense mechanism against infections in the upper respiratory tract was studied in 50 children with otitis media with effusion (O.M.E.). In the bacteriological study of the nasopharynx, the incidence of H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis and group A Streptococcus was about 46%, 24%, 20%, 12% and 8%, respectively. The incidence of these species in the cases with O.M.E. was higher than that in the cases with chronic tonsilitis or control cases. In 41 O.M.E. cases with alpha-streptococci (82%), the incidence of alpha-streptococci with inhibitory activity against 5 pathogens (H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis, group A Streptococcus) was examined. The detection rate of alpha-streptococcal strains with inhibitory activity against 5 pathogens derived from the nasopharynx in the cases with O.M.E. was significantly lower than that of the strain in the chronic tonsilitis cases and the control cases. Moreover, the detection rate of inhibitory alpha-streptococci from the nasopharynx was lower than that of from the tonsil. These findings suggest that the decline of inhibitory activity against pathogens by normal flora in nasopharynx is one of the factors causing O.M.E.

Child↗

Inhibition of mucociliary clearance of the eustachian tube by leukotrienes C4 and D4.

The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10(-8) mol/L and 10(-6) mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10(-5) mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eustachian tube.

Animals↗

[Relationship between orthostatic dizziness and/or giddiness, and hypotension in young normal females--a survey of 301 subjects].

Orthostatic dysregulation (OD) generally implies a systemic condition indicating poor circulatory function resulting from autonomic imbalance. It frequently appears in younger individuals at or around puberty, and is predominant in females. It is also known that individuals with this condition experience orthostatic dizziness and/or giddiness, fainting on standing and other various non-specific, subjective symptoms. Three hundred and one young normal females ranging in age from 18 to 21 years were examined using the Schellong test and the OD questionnaire to investigate the relationship between orthostatic dizziness and hypotension. Orthostatic dizziness and/or giddiness was the most frequent symptom, noted in 171 of 301 young subjects (56.8%), regardless of whether or not the subjects were actually diagnosed as having OD based on the questionnaire. Both low systolic blood pressure (90 mmHg or loss) in the supine position and systolic pressure decrease (11 mmHg or more) in the standing position during the procedure for the Schellong test were significantly related to the occurrence of orthostatic dizziness and/or giddiness. It may be reasonable to conclude from the present study that orthostatic dizziness is even more commonly observed in young normal female subjects than expected and correlates more closely with both hypotension and systolic pressure decrease in the standing position than previously thought. Thus, in our opinion, this testing procedure introduced by Schellong can be useful, and is clinically applicable to the assessment of orthostatic dizziness and/or giddiness and OD, since this test has the advantage of being simple enough to carry out in clinical practice.

Adolescent↗

Effect of ibudilast on ciliary activity of human paranasal sinus mucosa in vitro.

The effect of ibudilast (CAS 50847-11-5, 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine, KC-404), an anti-asthmatic drug, on ciliary beat frequency (CBF) of human paranasal sinus mucosa was examined in vitro. Ciliary activation was observed after a 10-min exposure to 4.6 x 10(-6) mol/l ibudilast. Ibudilast dose-dependently increase CBF at the concentrations ranging from 4.6 x 10(-7) mol/l to 4.6 x 10(-5) mol/l. Propranolol inhibited ciliary activity induced by ibudilast; however, neither indometacin nor verapamil affected the activation of ibudilast on CBF. Platelet activating factor (PAF) and Leukotriene D4 (LTD4) are chemical mediators inducing mucosal dysfunction and damage. Ibudilast prevented ciliary inhibition induced by PAF and LTD4. These findings indicated that ibudilast activates CBF and inhibits the effect of PAF and LTD4 on ciliated cells, and consequently improves the pathogenesis of allergic disorders such as the inhibited mucociliary transport system and airway hyperresponsiveness.

Bronchodilator Agents↗

The effects of leukotrienes C4 and D4 on ciliary activity of human paranasal sinus mucosa in vitro.

The effects of leukotrienes C4 and D4 on ciliary activity of human paranasal sinus mucosa were investigated in vitro. Normal mucosa was surgically obtained from human paranasal sinuses and incubated in the form of tissue culture. Ciliated cells were magnified under an inverted microscope, and ciliary activity was photoelectrically measured. LTD4 progressively inhibited ciliary activity, and showed a more potent effect on ciliary activity compared to LTC4. The concentrations of LTC4 and LTD4 in the incubation medium were determined by radioimmunoassay when the mucosa was incubated with 10(-8) M LTC4. The concentration of LTD4 gradually increased and after 90 min reached the maximum of 0.71 x 10(-8) M, while that of LTC4 was reduced to about 10% of its initial concentration within 60 min. These results suggested the possible conversion of LTC4 to LTD4 on the mucosa, and that LTC4 can inhibit ciliary activity by means of LTD4.

Cilia↗

Leukotriene D4-induced mucosal damage during long observation periods in vitro.

The effect of leukotriene D4 (LTD4) on human paranasal sinus mucosa was investigated for over 1 hour up to 24 hours using a VTR system at 2,500 X in vitro. Ethmoidal sinus mucosal specimens were incubated in tissue culture, and after exposure to LTD4 the mucosal surface profile was viewed under an inverted phase-contrast microscope equipped with a VTR system on a TVscreen. LTD4-induced ultrastructural alterations, ciliostasis, alterations consisted of a coarse profile and epithelial cell exfoliation. Ciliary activity was photoelectorically measured on the screen hourly. The mucosal specimens were morphologically examined before and after exposure to LTD4 by transmission electron microscopy. LTD4 inhibited ciliary activity in a time- and dose-dependent manner at concentrations ranging from 10(-6)M to 10(-10)M, whereas LTE4 had a minimal effect on the mucosa even at the concentration of 10(-6) M. Irrigation of the mucosa with culture medium after 5-min of exposure to 10(-8) M LTD4 delayed appearance of ciliary inhibition and alteration of the mucosal surface profile, but had no effect after 15-min exposure. These effects of LTD4 on the mucosa were blocked by preincubation with the LT antagonists, FPL-55712 and Ly-171883. These results demonstrate the cytotoxic effect of LTD4 on human airway epithelium in vitro.

Cilia↗

Clinical efficacy of Tranilast on otitis media with effusion in children.

In this open randomized study, we evaluated the efficacy of Tranilast, one of the anti-inflammatory drugs, on otitis media with effusion in children. Sixty-two patients (103 ears) were divided into two groups: Group A was given Tranilast and local treatment (nasal and tubal); Group B only received local treatment (control for Group A). The overall improvement rating assessed as "moderately improved or above" for Group A was 63.6%, Group B 47.9%. There was a significant improvement in Group A as compared to Group B (p < 0.05). In subjects who suffered from otitis media with effusion for over 2 months. Group A exhibited 50.0% of efficacy while Group B only 15.4% (p < 0.05).

Acoustic Impedance Tests↗

[Effect of 14-member lactone ring macrolides on anti staphylococcal activity and swarming ability of Pseudomonas aeruginosa].

The purpose of this report is to examine the effect of Macrolides (Erythromycin and Roxythromycin) on swarming ability and antistaphylococcal activity of Pseudomonas aeruginosa. The standard strain (ATCC27854) and clinically isolated P. aeruginosa were used as test strains. The influence of Macrolides on antistaphylococcal activity and swarming ability were determined by the agar plate dilution method. The antistaphylococcal activity of P. aeruginosa was not affected at the concentration of 1.56 micrograms/ml of both Erythromycin and Roxythromycin. But the antistaphylococcal activity was not observed at the concentration over 100 micrograms/ml. The swarming ability was not affected at the concentration up to 12.5 micrograms/ml. It has been proved that Macrolides reveal inhibition of virulent factors of P. aeruginosa such as protease, elastase, piocianin and so on. Furthermore our data revealed that Macrolides inhibited swarming ability of P. aeruginosa, and did not affect the antistaphylococcal activity of P. aeruginosa under 1.56 micrograms/ml concentration. Consequently, these results suggest that Macrolides have exhibited a previously unknown pharmacological effect, and may be of interest in that there may be bacterial interaction between MRSA and P. aeruginosa.

Anti-Bacterial Agents↗

Turn-over of PAF in cultures of human paranasal sinus mucosa.

The change of PAF concentration in the culture medium was investigated by radioimmunoassay when 10(-8) M PAF or 10(-8) M lyso-PAF was incubated with a piece of normal human paranasal sinus mucosa. The PAF concentration in the medium of the former group was halved within 11.3 min and reduced to less than 5% of the initial concentration within 60 min. However, there was no significant difference in the reduction of PAF concentrations in the medium between groups with or without the mucosa. When 10(-8) M lyso-PAF was incubated with a piece of mucosa, PAF gradually increased and reached the maximum of 0.36 x 10(-8) M at 20 min, and thereafter quickly decreased to a non-detectable level.

Cells, Cultured↗

[Phase I study of CGS16949A--a new aromatase inhibitor. Cooperative Study Group for CGS16949A].

Phase I study of CGS16949A--a new aromatase inhibitor--was performed in postmenopausal women with advanced breast cancer who received either single oral administration of 4 and 8 mg, or multiple oral daily administration of 1, 2, 4, 8 and 16 mg for 5.5 days. No side effects were observed after single dose administration of 4 mg and 8 mg of CGS16949A. In the multiple administration, one patient received 1 mg/day for 3 days complained of abdominal pain (Grade 2), but administration of CGS16949 A was continued despite of the pain. In order to assess the causal relationship of the drug with the abdominal pain, the number of patients in 1 mg/day group was doubled from 3 to 6 patients, but no side effects were observed in the remaining five patients. In addition, no side effects, including abdominal pain, were noted in the other 2, 4, 8 and 16 mg/day groups. After multiple administration, plasma concentrations of estradiol at 5 hrs after the final dosage in the respective dose groups were reduced to 47.1 +/- 8.3%, 37.3 +/- 3.0%, 28.0 +/- 7.8%, 26.0 +/- 11.3% and 26.6 +/- 13.8% respectively. Similar tendencies were observed in estrone plasma levels and urinary estrogens levels. In this study, the reduction of plasma estrogen levels was confirmed following administration of CGS 16949A. The clinical usefulness of this new aromatase inhibitor remains to be studied further.

Administration, Oral↗

Study on the metabolism of lyso-platelet activating factor (lyso-PAF) in human paranasal sinus mucosa. The cultured ciliated epithelium can convert lyso-PAF to PAF.

The conversion of lyso-platelet activating factor (lyso-PAF) to PAF in cultured paranasal sinus mucosa obtained from normal human subjects was studied. The PAF concentration in the medium was determined after addition of lyso-PAF. PAF became detectable at 10 minutes after the addition of 10(-8)M lyso-PAF, and reached a maximum concentration (3.25 x 10(-9)M) at 20 minutes. The PAF level then gradually declined to become undetectable at 60 minutes after addition of lyso-PAF. Thus PAF is very unstable having a half-life calculated to be 12.8 minutes with an elimination constant of k = 0.05377 minutes-1. In contrast, lyso-PAF is known to be a stable metabolite of PAF as well as a precursor of PAF. The results obtained from this study suggest that the turnover of lyso-PAF to PAF may play a role in evoking prolonged inflammation in target organs or tissues.

Cells, Cultured↗

[Effect of erythromycin on anti staphylococcal activity and dye production of Pseudomonas aeruginosa isolated from clinical materials].

Anti staphylococcal activity by Pseudomonas aeruginosa was investigated through the use of the reversed agar plate and the filter paper stamp methods. Investigation was also conducted on the dye production of different clinical isolates of Pseudomonas aeruginosa, the relationship between drug susceptibility and anti staphylococcal activity, and the influence of erythromycin on anti staphylococcal activity. Seventy four strains of Pseudomonas aeruginosa were prepared which included 20 strains from pus, 34 strains from sputum and 20 strains from urine. These were then inoculated with methicillin resistant Staphylococcus aureus (MRSA). They were then cultured for 48 hours by using the reversed agar plate and the filter paper stamp methods. Anti staphylococcal activity was observed in 16 strains from pus (80%), 19 strains from sputum (55.9%) and 8 strains from urine (40%). The Pseudomonas aeruginosa strains which have no pigment tended to show poor anti staphylococcal activity. Drug susceptibility was tested using PIPC, AMK, IPM, CFS and OFLX. The strains which showed resistance to OFLX tended to show poor anti staphylococcal activity. Erythromycin inhibited the dye production of Pseudomonas aeruginosa but exhibited no effect on anti staphylococcal activity. Consequently, these results suggest erythromycin has exhibited a previously unknown pharmacological effect, furthermore, anti staphylococcal activity was not caused by pigmentation only.

Erythromycin↗

Neurotransmitter-induced exocytosis in goblet and acinar cells of rat nasal mucosa studied by video microscopy.

To investigate the mechanism and neural control of the nasal secretion, we observed the isolated rat nasal mucosa by video-enhanced differential interference contrast microscopy. This technique allowed us to visualize abrupt changes of the individual granules leading to degranulation in the acinar cells and in epithelial goblet cells during secretory stimulation. This image provided evidence that exocytosis is the major mode for regulated secretion in the nasal acinar cells and goblet cells. Acetylcholine (ACh, 0.1-100 microM), substance P (SP, 0.1-10 microM), and vasoactive intestinal peptide (VIP, 0.1-1 microM) induced exocytotic responses and shrinkage of the acinus in a concentration-dependent manner. The effects of ACh (10 microM) on the acinus were clearly inhibited by atropine (5 microM), but the effects of SP (1 microM) and VIP (1 microM) were not. The acinar shrinkage always started before exocytosis, suggesting that the fluid secretion precedes the mucus release. In goblet cells, SP (1 microM) and ACh (10 microM) increased the frequency of exocytotic responses significantly, suggesting that these substances truly play the role of a neurotransmitter for nasal secretion. Histamine (HIST) induced no visible response. The effect of HIST on secretory cells may be neuronally mediated in vivo.

Acetylcholine↗

[Further study of Schellong testing in 152 young females].

Orthostatic dysregulation (OD) generally implies a systemic condition indicating poor circulatory function resulting from autonomic imbalance, which usually appears in a rather young population at or around puberty, predominantly in females. This condition can be recognized from the results of a questionnaire which has been proposed and prepared by the Pediatric OD Study Group of Japan as diagnostic criteria for OD. Schellong testing has also been developed as a screening method to determine OD or orthostatic hypotension. We carried out a survey and analyzed data collected with the questionnaire and Schellong test results among 152 young normal females ranging in age from 18 to 21 years in order to obtain the actual prevalence of OD in these subjects. Among 152 young normal females, 39 (25.7%) were confirmed to have OD based on the questionnaire. Although orthostatic dizziness was relatively common in this series of young females, regardless of the presence or absence of OD (90/152, 59.2%), this symptom, which is listed as one of the 5 major items on the questionnaire, was much more prevalent in subjects with OD (37/39, 94.9%). Similar prevalence patterns for fatigability or unexplained tiredness were also found in subjects with OD (28/39, 71.8%) when compared with total subjects (55/152, 36.2%). As for the positive rate of the Schellong test, subjects with and without OD showed 33.3% and 31.3%, respectively, and this difference was not statistically significant. There was, however, a highly significant difference in the fall in systolic pressure during the Schellong test procedure between subjects without OD and 10 subjects with OD in whom orthostatic dizziness frequently occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗