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T Horio

Publications and source records attributed to T Horio.

At least 73 records · Page 4Linked to original sources

Ultraviolet radiation-induced suppression of natural killer cell activity is enhanced in xeroderma pigmentosum group A (XPA) model mice.

Xeroderma pigmentosum group A gene-deficient mice easily develop skin cancers by ultraviolet radiation. Natural killer cells play an important part in tumor surveillance. To study whether ultraviolet radiation-induced suppression of natural killer cell function is involved in the high incidence of skin tumors in patients with xeroderma pigmentosum, we analyzed the number and activity of natural killer cells in ultraviolet B-irradiated xeroderma pigmentosum A model mice. The number of natural killer cells in peripheral blood significantly decreased after ultraviolet B-irradiation only in xeroderma pigmentosum A mice, but those in the spleen were not affected. As compared with the wild-type mice, the xeroderma pigmentosum A mice displayed a higher level of spontaneous splenic natural killer cell activity (10%-15% vs 3%) and inducible natural killer activity (30%-50% vs 20%-25%) after injection of polyinosinic:polycytidylic acid. At 24 h after the last irradiation of three and five daily consecutive exposures to 500 mJ per cm2-ultraviolet B, however, the natural killer activity in xeroderma pigmentosum A mice decreased to 60 and 30% of the preirradiated level, respectively, but it did not in the wild-type mice. The depression of natural killer activity in xeroderma pigmentosum A mice recovered to a normal level at 10 and 15 d after the last irradiation, respectively. The high incidence of skin cancers in xeroderma pigmentosum patients may be mainly due to a defect in the repair of ultraviolet-damaged DNA of cutaneous cells, and possibly also due to an intensified ultraviolet-induced immunosuppression. Moreover, the present study suggests that the enhanced ultraviolet-induced impairment of natural killer function could be partially involved in cancer development.

Animals↗

Evaluation of apoptotic cells induced by ultraviolet light B radiation in epidermal sheets stained by the TUNEL technique.

Two major components of epidermal cells, keratinocytes and Langerhans cells, are injured by ultraviolet light B radiation, resulting in sunburn cell (apoptotic cell) formation, impaired function, and a reduced number of Langerhans cells. Quantitative analysis of Langerhans cell damage is usually performed using epidermal sheets, whereas that of keratinocytes has been performed by counting the number of sunburn cells in vertical tissue sections. In this study we assessed the influences of ultraviolet light B radiation on epidermal cells by apoptotic cell formation, using murine epidermal sheets stained by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique. Ten to 75 mJ per cm2 of ultraviolet light B radiation induced apoptotic cells in abdominal skin of C3H mice. The cells were induced in 6 h after 50 mJ per cm2 of ultraviolet light B irradiation with the peak in number in 24 h, 18.8 +/- 5.0 per mm2 and 97.7 +/- 7.4 per mm2, respectively. One week later, the apoptotic cells were not visualized. As C3H/He, BALB/C, and C57BL/6 mice showed almost the same frequency of apoptosis in epidermal sheets from 50 mJ per cm2 ultraviolet light B-irradiated skin, the induction of the cells by ultraviolet light B radiation did not depend on the genetic trait of the mouse. Xeroderma pigmentosum type A gene-deficient mice, however, showed a greater induction of apoptotic cells (216.9 +/- 25.2 per mm2) by ultraviolet light B radiation than xeroderma pigmentosum type A wild-type mice (89.5 +/- 13.6 per mm2) and conventional mice. Pretreatment with a SPF 60 sunscreen agent was quite effective in reducing the induction of apoptotic cells. Using confocal laser scanning microscopy and double staining, 1.5 +/- 2.7% of apoptotic cells were Ia-positive cells in 24 h after 50 mJ per cm2 of ultraviolet light B radiation. Apoptotic Ia-positive cells were not observed 48 h after the radiation. On the other hand, no apoptotic dendritic epidermal T cells were observed in up to 75 mJ per cm2 of ultraviolet light B radiated skin. Thus, nearly all apoptotic cells were keratinocytes, and Langerhans cells and dendritic epidermal T cells appeared resistant to ultraviolet light B-induced apoptosis. Compared with the assessment in vertical tissue sections, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique with epidermal sheets appeared to be a more physiologically relevant method for quantitative evaluation of apoptotic epidermal cells induced by ultraviolet light B radiation.

Animals↗

Comparison of local and systemic induction of acquired disease resistance in cucumber plants treated with benzothiadiazoles or salicylic acid.

The accumulation of chitinase and its involvement in systemic acquired disease resistance was analyzed using acibenzolar-S-methyl and salicylic acid (SA). Resistance against scab (pathogen: Cladosporium cucumerinum) and the accumulation of chitinase were rapidly induced in cucumber plants after treatment with acibenzolar-S-methyl. In contrast, SA protected the plants from C. cucumerinum and the accumulation of chitinase was induced only on the treated leaves. The accumulation of chitinase in response to inoculation with the pathogen was induced more rapidly in cucumber plants previously treated with acibenzolar-S-methyl than in plants pretreated with SA or water. Thus, it appears that a prospective signal(s), that induces systemic resistance, can be transferred from leaves treated with acibenzolar-S-methyl to the untreated upper and lower leaves where systemic resistance is elicited. In contrast, exogenously applied SA is not likely to function as a mobile, systemic resistance-inducing signal, because SA only induces localized acquired resistance.

Amino Acid Sequence↗

Autonomic function in hypertensive patients with neurovascular compression of the ventrolateral medulla oblongata.

OBJECTIVE: To study whether abnormalities of autonomic function exist in patients with essential hypertension and neurovascular compression (NVC) of the medulla oblongata. SUBJECTS AND METHODS: We studied 25 untreated patients with essential hypertension (13 men and 12 women, 27-74 years old). High-resolution magnetic resonance imaging and magnetic resonance angiography were used to detect NVC. Twenty-four-hour ambulatory monitoring of blood pressure and electrocardiogram were performed, and the power spectrum of heart rate variability was analyzed. On a separate day, various autonomic activity tests, including mental stress, hand grip, cold pressor, and Valsalva maneuver were performed. Baroreflex sensitivity was calculated from changes of blood pressure and R-R interval during phenylephrine infusion. A clonidine suppression test was also performed, with measurement of plasma catecholamine levels. RESULTS: Fourteen of 25 patients (56%) had NVC (C group), and 11 patients did not have NVC (NC group). There were no significant differences in age, sex, family history, or duration of hypertension between the C and NC groups. Average 24-h systolic blood pressure was similar between the two groups, although 24-h diastolic blood pressure was higher in the C group than the NC group. Daytime, night-time, and 24-h heart rate was significantly higher in the C group than in the NC group. Night-time low frequency/high frequency ratio was slightly higher in the C group. Plasma norepinephrine levels were significantly higher (467 +/- 217 versus 299 +/- 122 pg/ml), and baroflex sensitivity was slightly lower in the C group than in the NC group. Responses of blood pressure and heart rate to mental stress, cold pressor, hand grip, Valsalva maneuver, phenylephrine infusion, and clonidine tests were not significantly different between the two groups. CONCLUSIONS: NVC of the medulla oblongata was frequently found in patients with essential hypertension. Patients with NVC appeared to have enhanced sympathetic nervous activity compared with those without the compression.

Adult↗

Cardiovascular and renal effects of adrenomedullin in rats with heart failure.

Plasma adrenomedullin (AM), a novel hypotensive peptide, has been shown to increase in heart failure (HF). This study sought to examine the cardiovascular and renal effects of intravenous infusion of AM in HF rats and sham-operated rats (control) using two doses of AM that would not induce hypotension. Rat AM-(1-50) was intravenously administered at rates of 0.01 (low) and 0.05 (high) microg. kg body wt-1. min-1. Low-dose AM increased urine flow (+21% in HF, +29% in control) and urinary sodium excretion (+109% in HF, +123% in control) without changes in any hemodynamic variables. In contrast, high-dose AM slightly decreased mean arterial pressure (-3% in HF, -5% in control) and significantly increased cardiac output (+20% in HF, +12% in control). Infusion of high-dose AM resulted in significant decreases in right ventricular systolic pressure (-11%) and right atrial pressure (-28%) only in HF rats. High-dose AM significantly increased glomerular filtration rate (+10% in HF, +16% in control) and effective renal plasma flow (+25% in HF, +46% in control) as well as urine flow and urinary sodium excretion. In summary, intravenous infusion of AM exerted diuresis and natriuresis without inducing hypotension and, in the higher dose, produced beneficial hemodynamic and renal vasodilator effects in rats with compensated HF.

Adrenomedullin↗

Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats.

We investigated the pathophysiological significance of adrenomedullin (AM) in the development of left ventricular hypertrophy (LVH). LVH was produced by aortic banding (AB) in rats. The left ventricular weight/body weight (LV/BW) ratio, ventricular AM peptide and mRNA levels, and hemodynamics were measured at 1, 3, 7, and 21 days after the operation. Both LV/BW ratio and ventricular AM levels showed a significant increase from 1 day after the operation in the AB rats versus the sham-operated rats. Both increased in a time-dependent manner. The ventricular AM levels correlated with the LV/BW ratio (r=0.76, P<0.01). The AM mRNA levels were highly expressed at 1 day after the operation in the AB rats but showed no difference from 3 to 21 days after the operation between the AB and sham groups. The plasma AM levels showed a peak at 1 day after the operation in both groups. Then, we treated AB rats with an angiotensin-converting enzyme inhibitor (quinapril) in 2 doses (1 and 10 mg. kg-1. d-1) for 21 days. The quinapril treatment attenuated similarly both the LV/BW ratio and the ventricular AM levels. We also assessed the effects of AM and hydralazine administration for 7 days on the LV/BW ratio and hemodynamics of AB rats. Both AM and hydralazine administration reduced the blood pressure by approximately 10% compared with the nontreated AB rats, but a reduction of the LV/BW ratio was observed only in the AM-treated group (P<0.05). These results suggest that ventricular AM levels are elevated by chronic pressure overload in a time-dependent manner concomitant with the extent of LVH and that AM may play a pathophysiological role in the development of LVH in chronic pressure overload.

Adrenomedullin↗

Increased hyperkinesis in noninfarcted areas during short-term follow-up in patients with first anterior acute myocardial infarction treated by direct percutaneous transluminal coronary angioplasty.

The time course and clinical significance of hyperkinetic wall motion (HWM) in a noninfarcted area in direct percutaneous transluminal coronary angioplasty (PTCA) has not been clearly demonstrated in patients with acute myocardial infarction (AMI). The objectives of this study were to examine the change in HWM during one-month follow-up after direct PTCA and determine its impact on the recovery of global left ventricular function. A total of 61 patients with first anteroseptal AMI and one vessel disease were evaluated. The paired left ventriculograms in the 30 degrees right anterior oblique view taken both at baseline and follow-up were analyzed by the centerline and area length methods. The severity of hypokinesis was expressed by mean regional wall motion (standard deviation/chord) in most hypocontractile 50% of chords respondable to left anterior descending coronary artery area and HWM by mean regional wall motion in most hypercontractile 50% of chords of noninfarcted area. HWM increased from 0.18 +/- 1.07 to 0.48 +/- 1.30 (p = 0.0608). The delta global ejection fraction (global ejection fraction at follow-up minus global ejection fraction at baseline) was correlated with both delta infarcted wall motion (infarcted wall motion at follow-up minus infarcted wall motion at baseline) and delta HWM (HWM at follow-up minus HWM at baseline) (r = 0.576, p < 0.0001, r= 0.383, p = 0.0036, respectively) during follow-up. Further, the delta global ejection fraction showed better correlation with delta (HWM + infarcted wall motion) [(HWM plus infarcted wall motion at follow-up) minus (HWM plus infarcted wall motion at baseline)] (r= 0.593, p < 0.0001). Direct PTCA resulted in the enhancement of HWVM, which contributed to the increase in the global ejection fraction with the recovery of infarcted wall motion.

Aged↗

Evaluation of adjunctive intracoronary administration of acetylcholine following intravenous infusion of ergonovine to provoke coronary artery spasm.

A dilemma arises in patients with chest pain or other symptoms suggestive of coronary artery disease but without significant coronary artery stenosis or spasm even after the spasm provocation test by either ergonovine or acetylcholine. Incremental doses of intracoronary acetylcholine (up to 100 micrograms for left coronary artery and 50 micrograms for right coronary artery) were administered when intravenous infusion of ergonovine 0.4 mg showed negative results. A total of 39 patients were studied. Provocation test was performed because of chest pain suggestive of coronary artery disease (n = 19), atypical chest pain (n = 6), post balloon angioplasty status (n = 6), silent ischemia (n = 4), Adams-Stokes syndrome (n = 3), and dead-on-arrival (n = 1). Characteristics of chest pain indicated variant angina (n = 11), rest angina (n = 4), and effort angina (n = 4). No electrocardiographic evidence of ischemia was detected before this test in any patient. Spasm was induced in 23 patients (59.0%) with complete obstruction in 7 (30.4%), diffuse vasoconstriction (90-99%) in 14 (60.9%), and focal spasm in 2 (8.7%). The patients with chest pain showed the highest positive rate of 78.9%. Further, the patients with atypical chest pain and miscellaneous reasons also revealed positive rates of 33.3% and 42.9%, respectively. One ventricular tachycardia and 2 atrial fibrillations occurred but terminated spontaneously. This test is useful for detecting spasm in a variety of patients in whom intravenous ergonovine infusion fails to induce spasm.

Acetylcholine↗

Chronic infusion of adrenomedullin reduces pulmonary hypertension and lessens right ventricular hypertrophy in rats administered monocrotaline.

A novel vasorelaxant peptide, adrenomedullin, its messenger ribonucleic acid (mRNA), and the mRNA for its receptor are highly expressed in the lung, suggesting that adrenomedullin may play a role in the regulation of the pulmonary circulation. We investigated whether the chronic infusion of rat adrenomedullin would affect pulmonary hypertension and right ventricular hypertrophy produced by the administration of monocrotaline. Four-week-old male Wistar rats received a single subcutaneous injection of 60 mg/kg monocrotaline and were then chronically and subcutaneously infused with rat adrenomedullin (PH + AM group, n = 8) or saline (PH group, n = 10) by an osmotic minipump for a period of 21 days. Plasma levels of adrenomedullin were significantly higher in the PH vs. the control group. The chronic infusion of adrenomedullin in rats with pulmonary hypertension increased the plasma levels of adrenomedullin to a value 94% greater than that of the control group and 55% greater than that of the untreated PH group. Chronic infusion of adrenomedullin significantly lessened the increase in right ventricular systolic pressure and the ratio of right ventricular weight to body weight seen after monocrotaline treatment. Histological examination revealed that adrenomedullin also attenuated the medial thickening of the pulmonary artery. These results suggest that chronic infusion of adrenomedullin attenuates the pulmonary hypertension and right ventricular hypertrophy seen in rats treated with monocrotaline.

Adrenomedullin↗

Effect of adrenomedullin on cAMP and cGMP levels in rat cardiac myocytes and nonmyocytes.

The purpose of the present study was to determine if cardiac myocytes and nonmyocytes secrete adrenomedullin, to investigate the effects of adrenomedullin on cAMP and cGMP levels in cardiac myocytes and nonmyocytes, to study the effect of calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) and adrenomedullin-specific receptor antagonist, adrenomedullin-(22-52) on response to adrenomedullin and CGRP. Neonatal (days 1-2) cardiac myocytes and nonmyocytes were prepared from the ventricle of Wistar rats. Not only cardiac myocytes, but also nonmyocytes secrete almost equal amounts of adrenomedullin into the media. Both adrenomedullin and CGRP increased the cAMP levels, not the cGMP levels, both in the myocytes and nonmyocytes. In myocytes, CGRP-(8-37), almost completely inhibited the adrenomedullin- and CGRP-induced cAMP formation. In nonmyocytes, CGRP-(8-37) completely inhibited the cAMP levels induced by adrenomedullin and CGRP. More profound antagonistic effect of CGRP-(8-37) on cAMP levels induced by adrenomedullin was observed in nonmyocytes than in myocytes. In contrast, antagonistic effect of adrenomedullin-(22-52) for adrenomedullin-stimulated cAMP formation was considerably less potent than CGRP-(8-37) both in myocytes and nonmyocytes. Adrenomedullin-(22-52) did not affect the cAMP formation induced by CGRP either in myocytes or nonmyocytes. These results suggest that myocytes and nonmyocytes secrete adrenomedullin and that adrenomedullin increases cAMP levels possibly via different receptors in myocytes and nonmyocytes.

Adrenomedullin↗

A novel fission yeast gene, tht1+, is required for the fusion of nuclear envelopes during karyogamy.

We have isolated a fission yeast karyogamy mutant, tht1, in which nuclear congression and the association of two spindle pole bodies occurs but the subsequent fusion of nuclear envelopes is blocked. The tht1 mutation does not prevent meiosis, so cells execute meiosis with two unfused nuclei, leading to the production of aberrant asci. The tht1(+) gene was cloned and sequenced. Predicted amino acid sequence has no significant homology to previously known proteins but strongly suggests that it is a type I membrane protein. The tht1(+) gene is dispensable for vegetative growth and expressed only in conjugating cells. Tht1p is a glycoprotein susceptible to endoglycosilase H digestion. Site- directed mutagenesis showed that the N-glycosylation site, as well as the COOH-terminal region of Tht1p, is essential for its function. A protease protection assay indicated that the COOH terminus is cytoplasmic. Immunocytological analysis using a HA-tagged Tht1p suggested that the protein is localized in nuclear envelopes and in the ER during karyogamy and that its levels are reduced in cells containing fused nuclei.

Amino Acid Sequence↗

Cockayne syndrome without typical clinical manifestations including neurologic abnormalities.

Although patients with mild symptoms of atypical Cockayne syndrome (CS) have been described, there has not been a report of a patient with CS whose only clinical manifestation was cutaneous photosensitivity. Cells from patients with CS show UV sensitivity, reduced recovery of RNA synthesis, but normal UV-induced unscheduled DNA synthesis. On the other hand, the patients with UV-sensitive syndrome have only cutaneous photosensitivity and skin freckles, whereas those cells respond to UV radiation in a similar fashion to the CS cells. We describe a patient with CS who showed only photosensitivity without typical clinical manifestations of CS, but his cells showed UV sensitivity, reduced recovery of RNA synthesis, and normal unscheduled DNA synthesis after UV radiation similar to CS cells. Furthermore, the patient was assigned to complementation group B of CS on the basis of the results of complementation analysis. The present report suggests that CS has a wider spectrum than that considered previously.

Adolescent↗

Aspirin-sensitive urticaria: provocation with a leukotriene receptor antagonist.

The diagnosis of two patients with aspirin-induced urticaria (AIU) was confirmed by oral provocation with aspirin, other non-steroidal anti-inflammatory drugs, and food additives. Low doses of a novel leukotriene (LT) receptor antagonist, ONO-1078 (ONO, Japan) induced urticaria in these patients, while the same doses of ONO-1078 did not provoke any eruptions in 10 normal healthy volunteers or five patients with aspirin-unrelated chronic urticaria. This is the first report that a selective LTD4/LTE4 receptor antagonist that is effective as an antiasthmatic agent evoked urticaria in patients with AIU. Our observation suggests that the pathogenesis of AIU depends on the stimulation of LT receptors. The accumulation of results of anti-LT therapy may provide clues to resolve the pathogenetic mechanisms of this disorder.

Administration, Oral↗

Influence of physical exercise on human preferences for various taste solutions.

The effects of physical exercise on preference for various sapid solutions was studied in 58 healthy university students. After 30 min of exercise using a bicycle ergometer at 50% VO2max (maximal oxygen uptake) intensity, a rating scale test on taste hedonic tone and the triangle test for taste absolute threshold were done. The test solutions were sucrose, NaCl, citric acid, caffeine and monosodium glutamate (MSG). Preference scale values for sucrose and citric acid increased after exercise, whereas the values for NaCl, caffeine and MSG were not changed. The absolute thresholds for all the sapid solutions did not differ for pre- and post-exercise. These findings indicate that in humans preference for sucrose and citric acid increase after physical exercise.

Adult↗

Photosensitivity reactions caused by lomefloxacin hydrochloride: a multicenter survey.

The photosensitivity effect of lomefloxacin hydrochloride (LFLX) was investigated in terms of patient background factors (sex, age, underlying disease, complications, history, occupation, and residential condition, etc.), treatment factors (daily dosage of LFLX, duration of treatment, total dose, concomitant drugs, and previous medication, etc.), and correlations among them. In 100 institutions throughout Japan, 4,284 patients were enrolled over a period of 2 years, beginning in October 1991, avoiding the accumulation of patients in any specific season. Since 8 patients did not visit again after enrollment, the clinical records of 4,276 patients were analyzed. Photosensitivity in 44 patients was found (1.03%), but the symptoms in most patients were not severe and improved after discontinuation of LFLX treatment. The photosensitivity reaction was more prevalent in patients who were 60 years of age and older with concomitant diseases and complications, in patients treated with a total amount of 20 g and more of LFLX for 30 days or longer, and in patients with a history of previous treatment with quinolone drugs. Although the incidence and degree of the photosensitivity reaction vary significantly among new quinolone drugs, every quinolone drug is potentially phototoxic. In particular, long-term use of LFLX should be avoided, and patients taking LFLX should be advised to abstain from prolonged exposure to sunlight.

Adolescent↗

Inhibitory effect of shofu-san, a Japanese kampo medicine, on neutrophil functions in vitro.

The effect of Shofu-san (TJ-22), an oral Japanese kampo medicine, on several inflammatory parameters of human neutrophils, including reactive oxygen species (ROS) generation, chemotaxis, and calcium concentration, [Ca2+]i in neutrophils was examined in vitro. In addition, ROS generated in a cell-free, xanthine-xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). TJ-22 significantly decreased neutrophil-generated O2-, H2O2 and OH. in a dose-dependent manner. The medicine also markedly inhibited neutrophil chemotaxis and [Ca2+]i in neutrophils. In addition, three kinds of ROS generated in the cell-free system was reduced in the presence of TJ-22. Our results indicate that TJ-22 may exert an anti-inflammatory action by inhibiting the neutrophil functions and scavenging ROS, leading to a reduction in oxidative tissue injury.

Calcium↗

The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation.

The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known to have no significant effect on the growth of Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in acne comedones. Linoleic acid significantly suppressed ROS generated by neutrophils. The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation. These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.

Acne Vulgaris↗

Establishment of a tissue culture system for hamster sebaceous gland cells.

BACKGROUND: A human sebaceous gland culture system is very useful in studying the functions of the sebaceous glands at the cellular level. On the other hand, the success rates for culture systems and the experimental results from these human culture systems exhibit significant fluctuations, depending on the condition of the donor skin. OBJECTIVE: The purpose of this study was to establish a stable culture system in order to investigate the functions of the sebaceous glands under uniform conditions. METHODS: Sebaceous glands from the auricles of 5-week-old hamsters were isolated and seeded onto a 3T3 cell feeder layer. The proliferation, lipid production and response to androgens of these sebaceous-gland-derived cells (SGDC) were then examined. RESULTS: The SGDC showed outgrowth, formed colonies and became confluent in a 35-mm dish culture after 14 days in primary culture. The amount of intracellular lipids significantly increased following the peak of the cell proliferation. The composition of the intracellular lipids from the hamster SGDC was identical to human SGDC, except that the hamster SGDC did not contain any squalene. Testosterone and 5alpha-dihydrotestosterone markedly stimulated the proliferation of these SGDC in a dose-dependent manner. CONCLUSION: This tissue culture system will be a useful tool for the study of sebaceous gland function at the cellular level.

3T3 Cells↗