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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 253 records · Page 14Linked to original sources

Immunotherapy affects the seasonal increase in specific IgE and interleukin-4 in serum of patients with seasonal allergic rhinitis.

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-gamma were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-gamma was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.

Adult↗

Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on the plasma levels of IR-GHRH in normal adults.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Adult↗

Possible involvement of placental proteases in bradykinin (BK) degradation.

The hydrolysis of bradykinin (BK) by human placental subcellular fractions and pregnancy sera was studied in the presence of inhibitors by measuring amino acids liberated from BK by high-performance liquid chromatography. The effects of the inhibitors DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the essential roles of the above three proteases in BK degradation: among the three proteases, kininase I and endopeptidase 24.11 appeared to be the most important in kininase action in the placenta microsomes, whereas kininase I and ACE appeared to be the most important in kininase action in the placental cytosol, lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical arterial blood, umbilical venous blood and maternal plasma revealed higher concentrations in the mother than in the fetus. The present data suggest that degradation of BK in the placenta and pregnancy serum might contribute to the gradient of BK between mother and fetus.

3-Mercaptopropionic Acid↗

Modification of proteoglycan synthesis by corneal stromal cells on co-culture with either epithelial or endothelial cells.

Corneal stromal cells, prepared from 2-day-old chicks and embedded in collagen gel on an insert dish, were co-cultured with corneal epithelial cells or endothelial cells on a fibronectin-coated companion plate. Cell growth and proteoglycan synthesis, as determined as the incorporation of [35S] sulfate and [3H] glucosamine, were examined for each cell type in both combinations. In comparison with single cultures, growth was affected little, while proteoglycan synthesis was appreciably altered in both combinations. Stromal and epithelial cells stimulated proteoglycan synthesis by each other, while endothelial cells stimulated the synthesis by stromal cells, but stromal cells reduced that by endothelial cells to some extent. Endothelial cells alone synthesized proteoglycans much more actively than did epithelial or stromal cells. Analysis of the radiolabeled proteoglycans revealed that endothelial and epithelial cells had different effects on proteoglycan synthesis by stromal cells: the former tended to increase keratan sulfate synthesis by stromal cells, while the latter tended to increase chondroitin sulfate/dermatan sulfate synthesis. Proteoglycan synthesis in the corneal stroma in vivo might thus be controlled by the balance between the antipodal actions of the epithelial and endothelial cell layers.

Animals↗

Natural course of serum-specific immunoglobulin E and immunoglobulin G4 for a span of eight years in untreated patients with perennial allergic rhinitis.

During the past two decades, considerable attention has been devoted to the clinical role of serum-specific IgE and IgG4 following immunotherapy. To definitely discuss the clinical role of serum-specific IgG4, we should know the natural course of serum-specific IgG4 in the untreated patient with allergic rhinitis. To our knowledge, however, no such kind of study can be found in the literature. Our present study focused on the long-term follow-up of serum-specific IgE and IgG4 in patients who were not treated with immunotherapy for perennial allergic rhinitis. They were scheduled to take no medication for their perennial nasal symptoms for 8 years. Serum-specific IgE and IgG4 in untreated patients with perennial allergic rhinitis never significantly change during the observation period. These data will be of great value for studies in serologic changes following active treatment for atopic diseases. Additionally, our study suggests that a reduction in serum-specific IgE and an increase in serum-specific IgG4 following immunotherapy are not the result of an immunotherapy-independent and age-related phenomenon but the result of active immunologic modulation by immunotherapy.

Adjuvants, Immunologic↗

Soluble intercellular adhesion molecule-1 level in sera is elevated in perennial allergic rhinitis.

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera was measured in some allergic disorders, but serum sICAM-1 levels in perennial allergic rhinitis remain to be determined. Our study was aimed at elucidating whether the serum sICAM-1 levels in patients with perennial allergic rhinitis are different from those in nonatopic healthy volunteers and whether immunotherapy can modulate sICAM-1 levels. Serum sICAM-1 was determined in 20 nonallergic volunteers and 137 patients with perennial allergic rhinitis by a sandwich enzyme-linked immunosorbent assay. Our study demonstrated that the level of sICAM-1 in untreated patients is significantly elevated, as compared with nonatopic subjects. Immunotherapy could decrease sICAM-1 in perennial allergic rhinitis, but this suppressive effect became apparent only after many years of immunotherapy. In patients on immunotherapy, a close correlation was observed between sICAM-1 and nasal symptom scores. To take these lines of evidence together, a decrease in sICAM-1 might be related to the working mechanism of immunotherapy, and serum sICAM-1 could be used to monitor the effect of immunotherapy.

Adult↗

Effect of immunotherapy on seasonal changes in serum-specific IgE and IgG4 in patients with pollen allergic rhinitis.

Serum specific IgE and IgG4 in 70 patients with seasonal rhinitis caused by Japanese cedar pollens were determined before and during the pollen season. Seasonal increase rate in specific IgE was significantly smaller in the immunotherapy patients than the pharmacotherapy patients, and seasonal increase in specific IgG4 was significant in the immunotherapy patients only. Seasonal increase rate in specific IgE was not significantly different between the patients who responded markedly to short-term immunotherapy and those who did not. On the other hand, seasonal increase rate in specific IgG4 was significantly different between them. In contrast, seasonal increase rate in specific IgE was significantly smaller in the patients who showed marked response to the long-term immunotherapy than those who did not show marked response to the long-term immunotherapy, but seasonal increase rate in specific IgG4 was not significantly different between them. In conclusion, our results suggest that modulation of specific IgG4 response and specific IgE response might be involved in the early and late symptom relief during immunotherapy, respectively. However, further studies might be necessary to definitively establish the clinical roles of specific IgE and specific IgG4 in immunotherapy.

Adolescent↗

Smoking and neovascular form of age related macular degeneration in late middle aged males: findings from a case-control study in Japan. Research Committee on Chorioretinal Degenerations.

AIMS: The risk of smoking habits for developing the neovascular form of age related macular degeneration (neovascular form of AMD) were studied by a case-control study in Japan. METHODS: 56 male patients with the neovascular form of AMD and 82 healthy male controls, aged 50 to 69 years, were enrolled. A self administered questionnaire provided necessary information for the study subjects. Questions on smoking included whether the study subjects have ever smoked or not, and if smoked, depth of smoke inhalation, use of extra filter, age at starting smoking, average number of cigarettes smoked per day, and duration of smoking. When a smoker had stopped smoking, age at cessation was also recorded. Unconditional logistic analysis was adapted to calculate age adjusted odds ratios and their 95% confidence intervals (CIs) for smoking related factors. RESULTS: Age adjusted odds ratio of developing the neovascular form of AMD was 2.97 (95% CI 1.00-8.84) for current smokers and 2.09 (0.71-6.13) for ex smokers, compared with non-smokers. All smoking habit/smoking history related variables such as use of extra filter, smoke inhalation level, age at starting smoking, duration of smoking, and Brinkman index were found to be significantly related to an increased risk of the neovascular form of AMD. CONCLUSIONS: Suggested is the strong possibility that cigarette smoking enhances the neovascular form of AMD risk in late middle aged males, though the magnitude of risk by smoking variables might be overestimated, in part, because of health oriented controls.

Aged↗

Voltage-dependent gating of ATP-activated channels in PC12 cells.

The possibility that P2X receptors exhibit voltage-dependent gating in a similar manner to nicotinic receptors was investigated in rat pheochromocytoma cells with the use of whole cell voltage-clamp techniques. In the presence of extracellular ATP, slowly activating inward currents were elicited by stepping from -50 mV to potentials more negative than -80 mV; these currents had a time constant of approximately 60 ms at -120 mV. This slowly activating component (as a fraction of the total ATP-induced current) increased with membrane hyperpolarization from -80 to -100 mV and was much increased when depolarizing prepulses were applied, although the time constant of activation was not altered by depolarizations. The fraction of the slowly activating current and its time constant were decreased as the ATP concentration was increased from 10 to 300 microM. Thus it has been demonstrated that voltage-dependent gating of ATP-activated channels does occur in PC12 cells, and that this gating is modified by agonist concentration. It is possible that such gating may serve as a postsynaptic mechanism to facilitate excitatory neurotransmission by contributing to the inward rectification of the ATP-activated currents.

Adenosine Triphosphate↗

Multiple primary malignant neoplasms associated with prostate cancer in 312 consecutive cases.

The relative risk for a second primary cancer after the diagnosis of prostate cancer and the prognostic impact of the association of multiple primary malignant neoplasms (MPMNs) in patients with prostate cancer were analyzed in a retrospective study. The development of MPMNs was examined in 312 consecutive patients who had been diagnosed with prostate cancer between 1966 and 1992. The population-based cancer incidence rates in Japan were utilized to calculate the expected number of MPMNs. Of the 312 patients, 60 fulfilled the diagnosis of MPMNs. In 13 men, prostate cancer and other malignancies were diagnosed simultaneously. In 35 of the 312 patients, prostate cancer was the second or third cancer diagnosis. In the remaining 287 patients, prostate cancer developed initially. Of the 287 patients, 12 developed a second primary malignancy compared with 17 expected (relative risk 0.71, 95% confidence interval 0.45-1.4). No single anatomic site showed a significantly increased risk above that expected either. The overall survival of patients with prostate cancer was not reduced by the association with MPMNs. This may be explained by the fact that the stage of the prostate cancer was lower in patients with MPMNs than in patients without MPMNs.

Adenocarcinoma↗

Significant correlation between symptom score and IgG4 antibody titer following long-term immunotherapy for perennial allergic rhinitis.

Although there is evidence of some measure of clinical benefit as well as immunologic change during the early phase of immunotherapy, a sustained clinical response is only possible with prolonged therapy. Immunotherapy has to be administered for about 3 to 5 years for such sustained clinical efficacy. This study aimed at investigating the dynamics of IgE and IgG4 antibodies after more than 5 years of immunotherapy, to examine the statistical correlation between these antibodies and symptom scores. Our study demonstrated that the allergen-specific IgE antibody level significantly decreases and the IgG4 antibody level significantly increases following immunotherapy. However, the percent decrease in IgE antibodies did not correlate with the percent decrease in symptom scores. On the other hand, the percent increase in IgG4 antibodies correlated with the percent decrease in symptom scores. We infer that an elevation of IgG4 antibodies is not simply an epiphenomenon unrelated to the underlying working mechanism of clinically successful immunotherapy, but probably makes an active contribution to symptom relief.

Adolescent↗

Effect of immunotherapy on serum levels of eosinophil cationic protein in perennial allergic rhinitis.

Eosinophil cationic protein (ECP) levels in the serum of clotted blood could reflect the rate of activation of circulating eosinophils. We investigated the serum ECP levels in patients with perennial allergic rhinitis, with special reference to the effect of immunotherapy on the serum ECP levels. Serum ECP levels in untreated patients with perennial allergic rhinitis are significantly higher than those of nonatopic volunteers. Therefore, this elevation in the untreated patients represents an ongoing inflammation occurring in allergic rhinitis. The mean serum ECP level of a 1-year immunotherapy group was significantly higher than that of the nonatopic group, and was not different from that of the untreated group. In contrast, the mean serum ECP level in patients who had more than 2 years of immunotherapy was significantly lower than that of the untreated group, and was not different from that of the nonatopic group. Additionally, serum ECP levels were significantly correlated with the duration of immunotherapy. These findings suggest that activation of circulating eosinophils decreases gradually during immunotherapy, but this inhibition becomes apparent only after 2 years of immunotherapy. The control of circulating eosinophil activation might be one of the important working mechanisms behind the clinical effect of immunotherapy.

Adolescent↗

In vitro conversion of 2,3-oxidosqualene into dammarenediol by Panax ginseng microsomes.

(RS)-[3-3H]-2,3-Oxidosqualene (1) was converted into (20S)-dammarenediol (2) and not to (20R)-dammarenediol by a microsomal fraction prepared from the hairy root of Panax ginseng. The enzyme activity was highest at pH 6.0 and was not increased by the addition of any detergents. These properties differed significantly from those of other 2,3-oxidosqualene cyclases reported from higher plants and animals.

Cyclization↗

Effects on fetal growth of repeated blood collection for toxicokinetics from pregnant rats.

Repeated blood collection from pregnant rats was examined for effects on fetuses. Blood was collected four times from the same pregnant rat (0.5 ml each time and 2 ml in total). In Experiment 1, blood was first collected on day 9 of gestation and then repeatedly at 1, 4 and 18 hr intervals. In Experiment 2, blood was collected once on day 6 of gestation and then repeatedly on days 9, 12 and 15. Decreases in body weight and food consumption of the pregnant animals were noted in both experiments and considered due to restraint and needle puncture. In neither experiment could any effects be found on day 20 of gestation with regard to viability, fetal weight, placental weight or gross malformation. The results indicated that this regimen of blood collection could be used in developmental toxicity assessment studies.

Animals↗

Estimated prevalence and incidence of adult Still's disease: findings by a nationwide epidemiological survey in Japan.

To estimate prevalence and incidence of adult Still's disease in Japan, and to describe the epidemiological features of the patients, a nationwide epidemiological survey was conducted in 1994. The study consisted of two questionnaires which were distributed to the heads of the relevant departments, randomly sampled, in hospitals throughout Japan. Following major epidemiological findings emerged from the study: (a) The total annual number of patients treated for adult Still's disease was estimated as 1,100 in 1993 in Japan. The estimated crude prevalence among those aged 16 years or older were calculated as 0.73 and 1.47 per 100,000 population for males and females, respectively, with the corresponding crude incidence rate of 0.22 and 0.34. (b) The sex ratio (female to male) of the reported patients was 2.1. This female predominance might be specific to Japan, though additional surveys in other countries will be warranted. The mean age of the patients was 38.1 years, and female patients tended to be older than male ones; 50% of the female patients aged 40 years or older, while so did only 28% of the male patients.

Adolescent↗

Smoking habits, local brand cigarettes and lung cancer risk in Okinawa, Japan.

To disclose the association between smoking habits and lung cancer in Okinawa, Japan, we analyzed the data from a case-control study conducted from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (a) The odds ratios (ORs) for current smokers relative to nonsmokers were much greater for squamous cell carcinoma than for adenocarcinoma. The OR was 9.82 for squamous cell carcinoma and 2.18 for adenocarcinoma in males, 28.2 and 1.14, correspondingly, in females. (b) Males who quit smoking for 20 years or more demonstrated no elevated lung cancer risk. (c) Among male current smokers, the more the number of cigarettes smoked per day, the higher the lung cancer risk for both cell types, but particularly for squamous cell carcinoma. In contrast, deep smoke inhalation significantly increased the risk for adenocarcinoma in particular. (d) Okinawan brand cigarettes were more strongly associated with the risk, compared with other brand ones. This finding might partly explain the higher frequency of lung cancer in males with the relatively lower smoking rate in Okinawa.

Adenocarcinoma↗

Transcranial assessment of maternal cerebral blood flow velocity in patients with pre-eclampsia.

BACKGROUND: To clarify the cerebral hemodynamics in pre-eclamptic pregnant women, we investigated the blood flow velocity of the cerebral arteries. METHODS: The mean blood flow velocity and pulsatility index (PI) of the middle cerebral artery (MCA) and internal carotid artery (ICA) in normal pregnant women (n = 35) and pre-eclamptic patients (n = 18) were examined transcranially using pulsed-wave Doppler technique with a 2 MHz probe. In two pre-eclamptic women with post-partum visual disturbance, we examined the mean blood flow velocity and PI of the MCA and ICA every day. RESULTS: The mean blood flow velocity of the MCA in the pre-eclamptic patients (89.7 +/- 20.5 cm/s) was significantly higher than that in the normal pregnant women (53.6 +/- 16.9 cm/s) (p < 0.05). PI of the MCA in the former group (0.67 +/- 0.13) was significantly lower than that in the latter (0.78 +/- 0.02) (p < 0.05). There was no significant difference between these two groups in these variables of the ICA. In the two patients with visual disturbance, the mean blood flow velocity of the MCA was increased before the onset of visual disturbance and decreased gradually following the disappearance of this symptom. In these patients, spasm of the MCA was confirmed by magnetic resonance angiography. CONCLUSIONS: In pre-eclamptic patients, we found increased MCA mean velocity before the onset of visual disturbance. Transcranial Doppler may be useful for the evaluation of cerebral hemodynamics and the prediction of eclampsia.

Adult↗