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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 199 records · Page 11Linked to original sources

Aberrant interleukin-2 receptor-mediated blastoformation of peripheral blood lymphocytes in a severe major depressive episode.

BACKGROUND: We examined interleukin-2 (IL-2) related immune pathways in depression to elucidate mechanisms underlying various immunological disturbances associated with depression. METHODS: Subjects comprised 35 unmedicated patients with a major depressive episode without psychotic features and 36 age- and sex-matched healthy volunteers. The immune parameters examined included the numbers of B and T cells, IL-2 receptor-mediated blastoformation (IL-2R-mediated blastoformation), IL-2 production and expression of the IL-2 receptor alpha-subunit. RESULTS: The patients with a severe episode showed significantly lower IL-2R-mediated blastoformation than the controls. There was a statistically significant negative correlation between IL-2R-mediated blastoformation and the severity of depression at the time of entry. CONCLUSION: The reduced IL-2R-mediated blastoformation may partly explain several previously reported abnormal immune functions associated with depression.

Acute Disease↗

Seasonal rise in interleukin-4 during pollen season is related to seasonal rise in specific IgE for pollens but not for mites.

Since IL-4 plays a key role in inducing and increasing the generation of not only primary polyclonal but also secondary specific IgE responses by B lymphocytes, a seasonal increase in IL-4 is likely to be involved in such seasonal rises in specific IgE in seasonal allergic rhinitis. The first aim of this study was to investigate the possible seasonal increase in serum IL-4 in patients with seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases in response to seasonal pollen exposure and is responsible for the seasonal increase in pollen-specific IgE in sera, this increase in IL-4 might theoretically affect specific IgE synthesis for other allergens. The second aim was to investigate the effect of natural pollen exposure on serum concentrations of house dust mite-specific IgE in patients who have seasonal allergic rhinitis and concurrent perennial allergic rhinitis due to house dust mites. This study included 55 adult patients with seasonal and perennial allergic rhinitis due to Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood was collected twice from each patient, before and during the cedar pollen season 1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in sera. Both IL-4 and pollen-specific IgE in sera were significantly increased during the pollen season, and the seasonal increase rate in pollen-specific IgE was significantly correlated with the seasonal increase rate in IL-4. By contrast, D. farinae-specific IgE was not changed during the pollen season in these patients. In conclusion, an elevation of IL-4 in sera during the pollen season may play an important part in the seasonal rise in pollen-specific IgE, and enhancement of specific IgE synthesis is likely to need not only an increase in IL-4 but also an increase in the number and/or capacity of specific IgE-secreting B cells.

Adolescent↗

Soluble vascular cell adhesion molecule-1 in perennial allergic rhinitis.

Since the expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells plays a central part in the selective recruitment of eosinophils into allergic inflammatory lesions, VCAM-1 may be a key molecule in allergic inflammatory diseases. Soluble forms of VCAM-1 (sVCAM-1) have recently been identified in the circulation, but there is limited published information on levels of sVCAM-1 in the circulation. If the levels of sVCAM-1 vary between patients with allergic diseases and normal controls, this variance would be very useful to investigate the state of the allergic disease and underlying inflammation. This study investigated the serum sVCAM-1 level in patients with perennial allergic rhinitis (rhinitis group) in comparison with non-atopic healthy volunteers (control group). No significant difference in the serum sVCAM-1 level was seen between the two groups (p = 0.4342). However, the serum sVCAM-1 levels in the severe rhinitis group were significantly higher than those in both the control group (p = 0.0067) and the mild rhinitis group (p = 0.0015), whereas no significant difference was observed between the mild rhinitis group and the control group (p = 0.1113). In addition, the serum levels of sVCAM-1 were significantly correlated with the nasal symptoms in the rhinitis group (rs = 0.486, p < 0.0001). In conclusion, serum concentrations of sVCAM-1 are increased in patients with severe perennial allergic rhinitis, and measurement of sVCAM-1 concentrations in sera is likely to be a useful tool for investigation of the severity of allergic rhinitis and underlying inflammatory reactions.

Animals↗

Immunotherapy decreases seasonal rise in serum-soluble CD23 in seasonal allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating IgE synthesis, but the in vivo physiologic significance remains to be established. This study investigated the seasonal changes in sCD23 in patients with seasonal allergic rhinitis. It included 112 adult patients with seasonal allergic rhinitis due to Japanese cedar pollens and 20 nonatopic healthy volunteers. The 64 patients of the pharmacotherapy group were treated with nonsedating antihistamine tablets alone throughout the pollen season and the remaining 48 patients of the immunotherapy group continued to be treated with immunotherapy. Serum concentrations of sCD23 were measured in each patient, before and during the pollen season of 1996, by a sandwich enzyme-linked immunosorbent assay. The serum levels of sCD23 in the pharmacotherapy group before the pollen season were significantly higher than those in the nonatopic group (P = .0130) and those in the immunotherapy group (P = .0316). Seasonal increase in sCD23 was significant in the pharmacotherapy group, irrespective of the clinical response (P < .0001). By contrast, sCD23 was not significantly increased in the good responders to immunotherapy (P = .1826), but was significantly increased in the poor responders to immunotherapy (P = .0052). A significant correlation between seasonal increase in rate in specific IgE and seasonal increase in rate in sCD23 was confirmed in both the pharmacotherapy group (rs = 0.321, P = .0107) and the immunotherapy group (rs = 0.474, P = .0012). In conclusion, seasonal rise in sCD23 is associated with and is probably involved in seasonal rise in specific IgE in patients with seasonal allergic rhinitis, and successful immunotherapy is capable of blunting seasonal increase in sCD23, thus resulting in attenuation of seasonal increase in specific IgE and clinical benefits during the pollen season.

Adult↗

Effects of platelet activating factor on the tubotympanic mucosa and inner ear in the guinea pig.

The effect of platelet activating factor (PAF) was studied to elucidate its role in the pathogenesis of otitis media and sensorineural hearing loss. The PAF alone did not induce a reduction of ciliary activity of the cultured middle ear mucosa. However, a dose-dependent decrease in ciliary activity was observed in the presence of the medium containing both PAF and macrophages. Intravenous injection of PAF did not induce dysfunction of the mucociliary system or morphologic changes of epithelium in the tubotympanum, but cytoplasmic vacuolization and ballooning were observed in the inner ear within 1 hour after injection of PAF. In contrast, intratympanic injection of PAF induced mucociliary dysfunction and some pathologic changes in the tubotympanum. Intratympanic inoculation of PAF induced no pathologic findings in the inner ear. These results suggest that PAF is at least partially involved in the pathogenesis of certain middle ear diseases such as otitis media with effusion. Additionally, PAF might be involved in the pathogenesis of some types of unexplained sensorineural hearing loss.

Animals↗

Butyrate enhances interleukin (IL)-8 secretion by intestinal epithelial cells in response to IL-1beta and lipopolysaccharide.

Intestinal epithelial (Caco-2) cells secrete the chemokine, IL-8, after stimulation with IL-1beta, but not after lipopolysaccharide. Butyrate is a short chain fatty acid derived from the metabolism of intestinal contents by gut bacteria. Butyrate concentrations reflect, therefore, the bacterial microenvironment established within the intestine. We hypothesized that butyrate may alter the secretion of IL-8 by intestinal epithelial cells in response to stimulation by IL-1beta or lipopolysaccharide. Caco-2 cells were incubated in varying concentrations of sodium butyrate (0-20 mM) for 24 h before stimulation with lipopolysaccharide or IL-1beta. IL-8 secretion was measured over 24 h by ELISA. IL-8 mRNA accumulation was detected by Northern blots. Lipopolysaccharide induced the secretion of IL-8 only after Caco-2 cells cells had been cultured with sodium butyrate. Furthermore, butyrate significantly enhanced IL-8 secretion by cells stimulated with IL-1beta. Butyrate also increased IL-8 mRNA accumulation in stimulated Caco-2 cells. Intestinal epithelial cells can, therefore, be primed by butyrate to become activated by lipopolysaccharide and proinflammatory cytokines. This may represent a mechanism by which intestinal epithelial cells can regulate intestinal inflammation in response to changes in the intestinal milieu.

Blotting, Western↗

Change of peripheral levels of pituitary hormones and cytokines after injection of interferon (IFN)-beta in patients with chronic hepatitis C.

Interferons (IFNs) are now in use worldwide for the treatment of chronic viral hepatitis. Unfortunately, various side effects of IFNs have been reported. Because cytokines, which include IFNs, can affect endocrine function, endocrinological abnormalities are sometimes observed in patients treated with IFNs. We examined the effects of IFN-beta on peripheral levels of pituitary and adrenal hormones and cytokines. Six million international units of IFN-beta dissolved in glucose solution was injected for 30 min. As a control study, glucose solution without IFN-beta was injected. Pituitary hormones (ACTH, GH, TSH, prolactin (PRL), LH, FSH, and arginine-vasopressin (AVP)), cortisol, and cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF), and interleukin-1 receptor antagonist (IL-1ra) were measured before and after IFN-beta injection. The study was carried out on 14 patients with chronic hepatitis type C who were under treatment with IFN-beta. All studies were performed when the patients were afebrile. None of the patients had any endocrine or autoimmune diseases. Plasma ACTH levels increased significantly at 60-120 min after IFN-beta injection compared with the levels before IFN-beta injection and in the control study using glucose injection. Plasma cortisol levels increased after IFN-beta injection, in parallel with plasma ACTH elevation. Serum GH levels increased significantly at 120 min after IFN-beta injection. All the increased hormones including ACTH, cortisol, and GH, were decreased at the end of the study-180 min after IFN-beta injection. Serum levels of TSH, PRL, LH, FSH, and AVP were not changed significantly by IFN-beta injection. Plasma IL-1 and TNF levels did not change after IFN-beta injection, while IL-6 and IL-1ra were elevated significantly. The increases in IL-6 and IL-1ra were gradual, reaching their peak levels at 180 min after IFN-beta injection. However there were no correlations between the hormones measured in this study and the levels of IL-6 or IL-1ra. It would seem that IFN-beta has direct or indirect stimulatory effects for ACTH and GH without mediation of the cytokines. These in vivo results are important for investigating the relationship between endocrine and cytokine systems in humans.

Adrenal Cortex Hormones↗

Effects of the novel tricyclic quinoxalinedione derivatives, SM-18400 and its analogs, on N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the isolated neonatal rat spinal cord in vitro.

We examined the effects of novel tricyclic quinoxalinedione derivatives, SM-18400 ((S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy)phenylcarbamoylmethy l]-6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate) and its analogs (i.e., ID-17263 and ID-17332), on the N-methyl-D-aspartate (NMDA) receptor-mediated polysynaptic reflex (PSR) in the isolated spinal cord of neonatal rats in vitro. Application of SM-18400 selectively suppressed the PSR activity in a concentration-dependent manner without affecting the monosynaptic reflex (MSR). Differential suppression of the PSR was also obtained with ID-17263, ID-17332 and other known NMDA receptor glycine-binding site antagonists, 5,7-dichlorokynurenate (5,7-diClkyn) and L-689,560 (4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4 -tetrahydroquinoline). Relative potencies of the test drugs for inhibition of the PSR were as follows: SM-18400 >> L-689,560 > ID-17332 > ID-17263 > 5,7-diClkyn. In addition, the inhibitory effects of SM-18400 on PSR were markedly antagonized by simultaneous application of D-serine, an agonist for NMDA receptor glycine-binding sites. These findings suggest that SM-18400 is a potent NMDA receptor glycine-binding site antagonist and blocks the NMDA receptor-mediated synaptic neurotransmission in the spinal cord in vitro.

Aminoquinolines↗

[Characteristics of medical institutions visited by patients with intractable diseases--analyses of patients receiving financial aid for treatment].

The Research Committee of Epidemiology of Intractable Diseases (Ministry of Health and Welfare, Japan) conducted a nationwide survey of 34 intractable diseases. Each of 47 prefectural governments reported information on all patients with the diseases who received financial aid for the disease from April 1992 to March 1993. Information collected on each patient included the identification number, sex, age, the code of the municipality where the patient lived, and the medical institution and department where the patient was being treated. Out of 247, 726 patients whose information was reported by prefectural governments, we analysed data of 208,945 patients whose medical institutions were reported. The results can be summarized as follows: 1) Aged patients and children who were less than ten years old tended to visit medical institutions located in their neighborhoods and be treated in small hospitals or clinics. 2) The proportion of patients who visited hospitals with 200 beds or more was 77 percent. 3) Patients with the diseases resulting in physical disabilities such as SMON and malignant rheumatoid arthritis tended to visit clinics. Patients with skin diseases as pemphigus, epidermolysis bullosa and pustular psoriasis tended to be treated in university hospitals. 4) Many patients living in prefectures near large cities such as Tokyo and Ishikawa visited medical institutions in the large cities. 5) The proportion of patients who visited university hospitals decreased during the eight years from 1984 to 1992. However, a quarter of these patients visited university hospitals.

Adolescent↗

Estimated number of patients with chronic renal failure but not with end-stage renal disease in Japan: comparisons between two estimation methods.

We estimated the number of patients with chronic renal failure (CRF) but not with end-stage renal disease (ESRD) in Japan by two methods: a nationwide survey and an estimation using incidence rates of ESRD among CRF patients as well as the number of incident ESRD. The former estimated the number of patients with CRF but not with ESRD as 154,000 (95% confidence interval 139,000-168,000), while so did the latter as 142,000 (133,000-150,000). It follows that the number of CRF patients including ESRD could amount to more than 300,000, which would give a substantial impact on public health in Japan. Despite some own methodological issues in estimation, the two estimates were reasonably in good agreement: supporting their methodological validity in estimation, since sources of errors appeared to be quite independent of each other.

Adult↗

Descriptive epidemiology of pancreatic cancer in Japan.

This paper aimed to explore descriptive epidemiological features of pancreatic cancer in Japan, by examining secular trends in mortality (1950-1995) and incidence rates (1975-1991), and also to discuss background factors possibly ascribable to the recent variation in mortality and incidence rates. The age-adjusted mortality rate (adjusted by the 1985 model population) has increased by approximately 9-fold in both males (from 1.4 to 12.5 per 100,000 population) and females (from 0.8 to 6.8 per 100,000 population) between 1950 and 1995. But it began to level off in both sexes since 1985. The age-adjusted incidence rate has remained plateau in both sexes, but likely showed a downward trend since 1988 in females. The older age groups showed the most steep increasing gradient in both age-specific mortality and incidence rates in both sexes, whereas a little or no apparent increase was observed in young age groups. Diagnostic improvement and increased cigarette consumption were believed to be the two major factors contributing to the increased mortality and incidence rates in Japan, but further epidemiological studies will be required to clarify possible background factors for the recent levelling-off of the mortality and incidence rates.

Adult↗

[Result of treatment of squamous cell carcinoma of the tongue and floor of the mouth].

A statistical analysis was performed on 40 patients with squamous cell carcinoma of the tongue and mouth floor, which could be followed for 6 months or more after initial treatment in the Department of Otorhinolaryngology, School of Medicine, Keio University during the 14 years from 1983 to 1996. The 5-year survival rate determined by the Kaplan-Meier method for each stage was 100% for Stage I, 77.8% for Stage II, 60.0% for Stage III and 44.4% for Stage IV. Thirteen suffered a relapse after initial treatment and patients with relapses among them have all survived after the subsequent salvage surgery. In contrast, in nine patients with cervical relapse, however, the 5-year survival rate was 11.1% with an unfavorable prognosis. This confirmed that suppressing cervical relapses is important for treating tongue and floor mouth cancers. The treatment strategy in our department is characteristic of positive enforcement of prophylactic neck dissection in the surgery and introduction of neoadjuvant chemotherapy (NAC) in the chemotherapy. Prophylactic neck dissection was performed in the 17 patients and no relapse was observed on the side of prophylactic neck dissection. NAC was performed on 26 patients in consideration of suppressed minute metastases and preserved function and 24 determinable cases were statistically analyzed. Among patients who had received NAC, the oral function was successfully preserved without surgical intervention in six patients both patients who showed complete response (CR) and four out of 14 patients who had a partial response (PR) following NAC. This may indicate that the oral function could be preserved in those patients who exhibited CR following NAC, but that preservation could be difficult in patients who exhibited PR. In addition, concerning the accumulated 5-year survival rate in relation to the effect of NAC, responders (CR + PR) accounted for 90.9% and non-responders (no change + progressive disease following NAC) for 15.0% with a very good outcome noted in the responder group. These figures suggest that responders may have a significantly good prognosis in the multivariant analysis including additional background factors before treatment as well. Accordingly, the present therapeutic measures for non-responders must be reexamined and performed more carefully and accurately as compared with those for responders.

Adult↗

[Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate analysis of prognostic factors and evaluation of therapeutic modalities].

Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at Keio University Hospital between July 1981 and June 1996 were reviewed retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old, with an average age of 62.7. The primary lesion was located in the lateral wall in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14 (15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21 patients (23.1%). The patients were divided into two groups according to the initial main treatment of the primary lesion without regard to chemotherapy: 72 patients (79.1%) who received curative radiotherapy with or without salvage surgery, and 14 patients (15.4%) who underwent curative surgery with or without preoperative and/or postoperative radiation. The remaining 5 patients were treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%) received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by the Kaplan-Meier method as univariate analysis, and compared by the generalized Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five-year survival rates according to stage (UICC classification, 1987) were as follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30 cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p = 0.0274); and (3) location of primary lesion (p = 0.0400). The results of multivariate analysis by Cox's proportional hazards model identified T stage as a significant independent prognostic factor. Evaluation of the therapeutic modalities led to the following conclusions. (1) Differences in the initial treatments of the primary lesion were not reflected in the outcome. (2) Salvage surgery for residual or recurrent tumor contributed to improving the survival. The superior wall type, in particular, seemed to be a good indication for salvage surgery. (3) Although the limitations of radiotherapy are not defined clearly, we have to determine the indications for radical resection of tumors resistant to radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but there were no significant differences in survival between the group that underwent NAC and the other group in any other subset analyses. (5) Among the patients who underwent NAC, the responder (CR + PR) group showed a better five-year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but the difference was not significant.

Adult↗

Effect of intestinal helminth infection on some nutritional parameters among rural villagers in Nepal.

We report the prevalence of intestinal helminthiasis and its impact on health of Nepalese in two different rural Village Development Committees (VDC) in Nepal. A total of 261 school children from Okharpauwa VDC in Nuwakot district (Central Region) and 242 inhabitants of Boya VDC in Bhojpur district (Eastern Region) in Nepal were included in this study. The overall prevalence in these two different districts were 57.5% and 55.4%, respectively. Altogether four types of helminths were detected. In both districts, Ascaris lumbricoides was the commonest helminth. Mixed helminth infection in both study areas accounted for less than 5.0%. All helminth infected subjects were treated with a single dose of albendazole. Heavy Trichuris trichiura infection needed a second dose. Blood hemoglobin and serum total protein level in school children in Okharpauwa VDC increased significantly after chemotherapy (P < 0.05). Eosinophil count (10.1%; SD 5.0325) returned to normal (4.8%; SD 4.6997). Helminth infection in Boya VDC was more common in children than in adults. Serum total protein, albumin, total cholesterol and triglycerides levels were not influenced by the presence or absence of helminths among the inhabitants of Boya VDC. In both districts, more than 80.0% of the household had no latrine. In Boya VDC, 94.0% of inhabitants interviewed were not aware of other intestinal parasite other than A. lumbricoides.

Adolescent↗

[Estimated numbers of patients with intractable respiratory diseases].

To estimate the number of patients with intractable respiratory diseases, we conducted a two-stage nationwide epidemiological survey in 1997. The first survey was performed at randomly sampled hospitals to identify the number of patients treated. The second survey sought detailed clinico-epidemiological data on the patients reported in the first survey. The response rates were 54% for the first survey and 62% for the second. Based on the survey findings, we derived the following nationwide estimates: 450 patients (95% confidence interval: 360-530) with chronic thromboembolic pulmonary hypertension; 230 (200-260) with primary pulmonary hypertension; 180 (150-210) with obesity-associated hypoventilation syndrome; 40 (30-50) with primary alveolar hypoventilation syndrome; 160 (140-180) with histiocytosis X; and 190 (150-230) with juvenile pulmonary emphysema.

Chronic Disease↗

[NO2-/NO3- levels in blood and principal organs in rats treated with lipopolysaccharide].

It is well revealed that activation of macrophages stimulated by endotoxin resulted in induction of nitric oxide synthase which catalyze nitric oxide (NO) formation from L-arginine. Consequently, blood concentrations of NO2-/NO3- (NOx-) are shown to increase. We studied on pharmaco/toxicokinetics of NOx- in serum and principal organs in Wistar male rats after i.p. administrations of LPS and NaNO3. The serum levels of NOx- at 1 h and 6 h after nitrate administration (10 mg/kg, i.p.) were 240 and 120 microM, respectively. Tissue levels of NOx- in lung, liver and kidneys were ca.1/2 of the serum level. Those levels in spleen and brain were ca.1/4 and 1/10 of the serum level, respectively. The correlation of NOx- levels in serum and these 5 organ tissues between 1 h and 6 h after administration of nitrate was r = 0.992 suggesting no specific accumulation of NOx- in these organs. The serum level of NOx- at 18 h after LPS treatment (1 mg/kg, i.p.) was 430 microM. The correlation of NOx- levels in serum and 5 organ tissues between LPS and nitrate administrations was shown to be r = 0.851. NOx- levels of serum, lung, kidneys and brain showed good correlation but liver and spleen showed out of the correlation. The liver tissue level of NOx- after LPS treatment was low compared with the expected value from the serum level. The reason may be explained partially by the liver weight increase and the liver toxicity with increased GPT and gamma-GT levels due to LPS. Contrary to this, NOx- level of spleen tissue after LPS treatment was more than 2-fold compared with the expected value from the serum level suggesting NO formation in the spleen. This was supported by the markedly high concentration (73.2 nmol/g tissue) of NO2- in the spleen tissue. NO2- levels in lung (34.5 nmol/g tissue) and brain (14.3) were also found to be significantly high after stimulation with LPS suggesting NO formation in these organs. Increased formation of NO2- in these organs by LPS stimulation suggests the formation of active nitrogen oxides such as N2O3 which is an effective nitrosating agent in non-acidic conditions in vivo.

Animals↗