Biomedical subjects

Y Ohmoto

Publications and source records attributed to Y Ohmoto.

At least 91 records · Page 5Linked to original sources

PubMed1997

Efficacy of continuous subcutaneous infusion therapy using interferon alpha and the possible prognostic indicator of TNF-alpha in renal cell carcinoma.

BACKGROUND: In an attempt to improve efficacy by escalating the dose and maintaining higher serum concentrations over a long period of time, this study examines continuous interferon alpha (IFN alpha) subcutaneous infusion therapy in patients with renal cell carcinoma (RCC). METHODS: Seven of 11 patients with RCC had evaluable metastatic lesions. A highly purified natural human IFN alpha was injected subcutaneously via an infuser pump for 5 consecutive days, followed by a 2-day rest period (25 million IU/week). The treatment was continued for a period of 15 weeks. Serum concentrations of IFN alpha, IL-1 alpha, IL-1 beta, TNF-alpha, and IFN gamma were measured at intervals throughout the study period. RESULTS: Two of the 7 patients with evaluable lesions achieved a partial response (overall response rate, 29%), while 1 achieved a partial response only to lung metastasis. These 3 cases were defined as responders. No difference was found in the concentration of serum IFN alpha between responders and nonresponders, however, a significantly higher concentration of serum TNF-alpha was observed in responders (P < 0.05, Mann-Whitney U test). Five cases (45%) had moderate to severe adverse effects, including depression (n = 1), eyeground hemorrhage (n = 2), and general fatigue (n = 2). CONCLUSION: Appropriate patient selection may be necessary for subcutaneous continuous infusion therapy for the treatment of metastatic RCC. Also, the serum concentration of TNF-alpha measured during the course of treatment reflected well on the outcome of IFN alpha therapy.

Adult↗

PubMed1997

Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45.

Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription.

Gene Expression Regulation↗

PubMed1997

A specific elevation of RANTES in bronchoalveolar lavage fluids of patients with chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic lung disorder characterized pathologically by massive eosinophil infiltration into lung. In the bronchoalveolar lavage fluid (BALF) of patients with CEP, eosinophil numbers were markedly increased but returned to normal-levels upon the resolution of clinical symptoms, which suggests the crucial role of eosinophils in the pathogenesis of CEP. To clarify the mechanism of eosinophil accumulation in CEP, we determined the BALF levels of RANTES and macrophage inflammatory protein-1 alpha, two chemokines that predominantly exhibit in vitro eosinophil chemotactic activities. RANTES (106.7 +/- 27.2 pg/mg albumin; n = 16) concentrations in BALF from patients with CEP were significantly elevated in comparison with those of normal control subjects (1.4 pg/mg albumin; n = 13), whereas BALF macrophage inflammatory protein-1 alpha levels were not. In addition, eosinophils, lymphocytes, and macrophages in BALF were positively stained with a specific anti-RANTES antibody, which suggests that RANTES was produced locally in the lungs of CEP patients. Moreover, BALF-RANTES levels correlated significantly with the proportion of eosinophils in BALF. Furthermore, nearly half of the eosinophil chemotactic activities in BALF were abrogated by the anti-RANTES antibody in vitro. Collectively, these data suggest that locally produced RANTES is involved in eosinophil accumulation in the pulmonary alveolus and interstitium of patients with CEP.

Bronchoalveolar Lavage↗

PubMed1997

Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.

Human macrophage inflammatory protein-1 alpha (hMIP-1 alpha), also known as LD78, is a member of the chemokine/ intercrine family and an inhibitor of the proliferation of the hematopoietic stem cells in vitro. Using a specific monoclonal antibody, we observed significant localization of hMIP-1 alpha in eosinophilic myelocytes in human bone marrow. We further examined the expression of hMIP-1 alpha mRNA in human bone tissue by in situ hybridization. A high level of hMIP-1 alpha mRNA expression was detected in eosinophilic myelocytes in bone marrow, confirming these cells as the site of hMIP-1 alpha synthesis. hMIP-1 alpha mRNA expression was also detected in osteoblasts in the bone-remodeling sites, and osteoclasts were frequently observed in the vicinity of these osteoblasts. hMIP-1 alpha was also able to induce osteoclastogenesis on calcified matrices in the absence of any other osteotropic hormones. These results strongly suggest that hMIP-1 alpha is involved not only in the regulation of hematopoiesis but also in the modulation of bone remodeling.

Animals↗

PubMed1997

[Motor cortex stimulation therapy in patients with thalamic pain].

Seven patients with thalamic pain were treated by electrical stimulation of the motor cortex. Patients ranged from 55 to 71 years of age. There were six men and one woman. Causes of thalamic pain were thalamic infarction in 2 patients and thalamic hemorrhage in five. Six patients had intractable pain associated with dysesthesia in the upper and lower limb (upper limb dominant). One patient had intractable pain in the face contralateral to the lesion. Magnetic resonance images (MRI) were performed in 5 patients and showed the deposit of hemosiderin in the internal capsule, posterolateral nucleus and pulvinar. Electrodes were placed on the motor cortex epidurally in seven patients. Electrodes were implanted permanently in six patients and removed in one patient after an unsatisfactory result of test stimulation. Motor cortex stimulation provided satisfactory pain relief in all six patients for a month after the beginning of stimulation, however, by the time three months had passed, pain relief had become gradually unsatisfactory in five patients. We compared pain relief between 10 Hz and 100 Hz of stimulus rate in four patients and observed that all patients complained of fatigue in the upper extremity at the 100 Hz of stimulus rate, though no differences in pain relief was obtained according to which of these two stimulus rates were used. We concluded that motor cortex stimulation brought about pain inhibition in patients with thalamic pain, but pain control tended to become less gradual within several months after the beginning of stimulation.

Aged↗

PubMed1997

Age-related increase of autoantibodies to interleukin 1 alpha in healthy Japanese blood donors.

Although autoantibodies to interleukin-1 alpha (IL-1 alpha autoantibodies) are known to be present in sera of apparently healthy humans, their frequency of occurrence and significance are unclear. To determine the prevalence of detectable IL-1 alpha autoantibodies in normal human blood, we screened the plasma of blood donors (6290 subjects: 3977 men and 2313 women, ages 16 to 64 yr) by a radioimmununoassay which we developed using a method that could detect over 5 ng/ml. Moreover, we investigated immunoglobulin class of IL-1 alpha autoantibodies and also their function. IL-1 alpha autoantibodies were detected in 14.6% of the 6290 donors. Their frequency was higher in males than females (16.6% vs. 11.2%, p < 0.01) and increased with age in both sexes. The proportion of subjects with a high IL-1 alpha autoantibodies titers also increased with age. We showed that IL-1 alpha autoantibodies were of the IgG class and that they had neutralizing function to IL-1 alpha by receptor assay. Neutralizing activity was only shown in plasma with concentration of IL-1 alpha autoantibodies, the level of which was over 1000 ng/ml. The affinity of the IL-1 alpha autoantibodies in plasma was between 2.1 x 10(-10) and 1.2 x 10(-9) M (mean 6.4 x 10(-10)M). Our results provide a basis for comparison with IL-1 alpha autoantibodies prevalence between healthy states and disease states, and suggest that IL-1 alpha autoantibodies may play a significant role in modulating the effects of excessive IL-1 alpha at local site or in systemic regions.

Adolescent↗

PubMed1996

Interleukin-12 activates human gamma delta T cells: synergistic effect of tumor necrosis factor-alpha.

gammadelta T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium-stimulated monocytes activate cord blood gammadelta T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for gammadelta T cell activation in vitro: interleukin (IL)-1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor were examined. Recombinant human IL-12 stimulated gammadelta T cells, but not alphabeta T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL-12-primed gammadelta T cell numbers increased to a greater extent in the culture to which exogenous IL-2 (5 U/ml) was added. Anti-TNF-alpha monoclonal antibody inhibited IL-12-induced up-regulation of CD25 on gammadelta T cells, suggesting that endogenous TNF-alpha may play a role in IL-12-induced activation of gammadelta T cells. Recombinant TNF-alpha synergistically augmented IL-12-induced activation of gammadelta T cells. Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL-12 and TNF-alpha were produced by mycobacterial lysate-stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, gammadelta T cells can be quickly and antigen-nonspecifically activated by soluble factors including IL-12 and TNF-alpha, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.

Adult↗

PubMed1996

Atypical MRI findings in treatment-related leukoencephalopathy: case report.

A patient with acute myeloblastic leukaemia showed atypical findings on MRI following combination therapy including intrathecal methotrexate and radiation. MRI findings not previously been reported are ring as well as patchy enhancement, marked mass effect and lesions extending to the putamen and corpus callosum.

Adult↗

PubMed1996

Aortic dissection during directional coronary atherectomy.

Directional coronary atherectomy has been applied to aorto-ostial lesions with higher success and lower complication rates than conventional balloon angioplasty. Aortic injuries have been reported with this technique, most resulting from the tip of the catheter. In this report, an aortic dissection caused by the shaft of the directional coronary atherectomy catheter is described.

Aortic Dissection↗

PubMed1996

Synthesis of interleukin-1, interleukin-6, and basic fibroblast growth factor by human cataract lens epithelial cells.

PURPOSE: To assay the following cytokines in an incubation medium of cultured lens epithelial cells (LECs) derived from human cataracts: interleukin-1 alpha (IL-1), interleukin (IL-6), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF). SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: The anterior lens capsule with attached LECs was obtained by capsulotomy during cataract surgery and cultured. The incubation medium was changed on days 1 and 2 of culture and thereafter weekly up to 7 weeks. The media collected from a specific number of cultures at each medium change were pooled and assayed for cytokines by enzyme-linked immunosorbent assay. RESULTS: Interleukin-1 alpha was detected in one of the two pools of the 2 week cultures (207 pg/10(6) cells), in two of the three pools of the 3 week cultures (120 pg/10(6) and 139 pg/10(6) cells), and in one of the two pools of the 4 week cultures (111 pg/10(6) cells). Interleukin-6 was detected in one pool of the 1 week cultures (195 pg/10(5) cells) and in one pool of the 7 week cultures (81.6 pg/10(5) cells). Basic FGF was detected in the incubation media from three series of samples during the culture time course: 87 pg/ml in the 1 day cultures in the first series; 478, 310, and 269 pg/ml in the 1 day, 2 day, and 1 week cultures, respectively, in the second series; and 98 and 83 pg/ml in the 1 and 2 day cultures, respectively, in the third series. The TNF-alpha and EGF were not detected in any sample. CONCLUSION: After cataract surgery, IL-1, IL-6, and b-FGF may be produced in vivo by residual LECs, causing postoperative inflammation and LEC proliferation.

Cataract↗

PubMed1996

Effects of the cytokines on the proliferation of and collagen synthesis by human cataract lens epithelial cells.

AIMS: To assess the effects of the cytokines, interleukin-1 (IL-1), IL-1 receptor antagonist (IL-1ra), transforming growth factor-beta 2 (TGF-beta 2) and basic fibroblast growth factor (b-FGF), on the mitosis of and collagen synthesis by lens epithelial cells (LECs) of human cataracts. METHODS: The anterior lens capsule with attached LECs was obtained by capsulotomy during cataract surgery and cultured. The cultures at 2 to 3 weeks before confluency were used for the experiments. To quantify the mitosis and collagen synthesis, the incorporation of 3H-thymidine and 3H-proline, respectively, into the LECs was measured by a scintillation counter at 48 hours and 24 hours, respectively, after addition of the cytokine at various concentrations into the incubation medium. RESULTS: IL-1 and b-FGF increased the mitosis and collagen synthesis significantly, but IL-1ra significantly decreased the mitosis while leaving the collagen synthesis intact. TGF-beta 2 decreased the mitosis significantly, but increased the collagen synthesis significantly. CONCLUSION: These cytokines may play an important role in an autocrine or paracrine pathway in the proliferation of residual LECs after cataract surgery. Elucidation of the role of these cytokines may lead to the development of new therapies for the prevention of secondary cataract.

Adult↗

PubMed1996

Upregulatory effects of interleukin-4 and interleukin-13 but not interleukin-10 on granulocyte/macrophage colony-stimulating factor production by human bronchial epithelial cells.

Airway epithelial cells are known to produce a granulocyte/macrophage colony-stimulating factor (GM-CSF), which induces eosinophilic inflammation in bronchial asthma. Interleukin-4 (IL-4), IL-10, and IL-13 produced by Th2 cells are involved in the pathogenesis of bronchial asthma. To assess their contributions to airway inflammation, we examined their effects on GM-CSF production by bronchial epithelial cells. Human bronchial epithelial cells were obtained under bronchoscopy from 21 patients with various respiratory diseases and incubated with or without IL-4, IL-10, or IL-13. Then the GM-CSF concentrations in the cell-free supernatants were measured by enzyme-linked immunosorbent assay. Results showed that IL-4 and IL-13 stimulated GM-CSF production by the epithelial cells dose-dependently, whereas IL-10 did not. The eosinophil survival-stimulating activity in the culture supernatants was closely correlated with GM-CSF concentration and was neutralized by anti-GM-CSF antibody. Thus, IL-4 and IL-13 may contribute to airway inflammation by upregulating GM-CSF production by bronchial epithelial cells.

Adult↗

PubMed1996

Interleukin-1 receptor antagonist in pleural effusion due to inflammatory and malignant lung disease.

Interleukin (IL)-1 is a key cytokine in inflammatory reactions. To clarify the mechanism of inflammation in the pleural cavity, we investigated the contribution of IL-1 and its antagonism to inflammatory processes in the pleural cavity. Interleukin-1 receptor antagonist (IL-1Ra) levels as well as IL-1 beta and interferon-gamma (IFN-gamma) levels were measured by enzyme immunoassay in pleural effusions from 70 patients. Pleural macrophages were also examined as possible sources of these cytokines in 10 patients. IL-1Ra was detectable in 28 patients (40%) out of 70 patients with pleural effusions. Patients with tuberculosis had significantly higher IL-1Ra as well as IFN-gamma levels in pleural effusion than patients with lung cancer. Transudative pleural effusions had low or undetectable IL-IRa levels. On the other hand, IL-1 beta levels were low, except in cases of parapneumonic pleural effusion. Spontaneous production of IL-1Ra pleural macrophages was observed in six patients, and IL-4 significantly augmented its production. Although spontaneous production of IL-1 beta was observed in only two patients, pleural macrophages produced significant amounts of IL-1 beta in response to lipopolysaccharide in all 10 patients examined. These results suggest that interleukin-1 receptor antagonist regulates various reactions by interleukin-1 in pleural effusion, and that pleural macrophages may act in situ as a source of interleukin-1 receptor antagonist.

Adult↗

PubMed1996

Familial occurrence of electrocardiographic abnormalities of the Brugada-type.

Electrocardiographic abnormalities were pointed out in a 51-year-old Japanese male whose major complaint was dizziness. His electrocardiogram showed a complete right bundle branch block, and a prolonged His bundle-ventricle (HV) interval of 100 msec. Two members of his family died of heart disease and 3 members, including a case of sudden death, presented an abnormal electrocardiogram of the Brugada-type with persistent ST segment elevation in the right precordial leads and right bundle branch block. The signal-averaged examination was made in the children of cases that died with the diagnosis of sudden death. Four cases showed a tendency of delay in the HV interval and a positive finding in the late potential. Further studies are necessary to clarify the relationship between electrocardiographic abnormalities of the Brugada-type and atrioventricular conduction disorder as well as to clarify the genetic basis of this disorder.

Adolescent↗

PubMed1996

Plasma M-CSF as an indicator of response to chemotherapy in adult T cell leukemia patients.

The plasma concentration of macrophage colony-stimulating factor (M-CSF) was measured in 10 patients with acute type adult T cell leukemia (ATL) during the clinical course before and after chemotherapy. M-CSF concentration decreased significantly when the patients achieved complete remission (CR) or partial remission (PR) (t-test: p = 0.0001). Five of the patients showed disease progression after several months of PR, and plasma M-CSF increased at that time (t-test: p = 0.0456). Thus, plasma M-CSF concentration appeared to accurately reflect the disease activity in ATL. In support of these results, all three ATL cell lines established from these patients secreted M-CSF in vitro after stimulation with phorbol myristate acetate (PMA) or concanavalin A (Con A). Plasma M-CSF concentration, however, increased transiently when the patients were febrile (t-test: p = 0.0001), even though their ATL condition was unchanged. Taken together, these results indicate that there are two sources of increased plasma M-CSF concentration in ATL; ATL cells themselves and normal parenchymal cells that cause this increase as the result of elevated body temperature due to inflammation.

Adult↗

PubMed1996

Features of the cytokines secreted by adult T cell leukemia (ATL) cells.

Adult T cell leukemia (ATL) cells show a mature helper-inducer T cell phenotype and are thought to secrete many kinds of cytokines in vivo, complicating the clinical features in these patients. In an attempt to specify the cytokines produced by ATL cells, we measured the cytokine concentration in the culture supernatants of three ATL cell lines, all of which were confirmed to be true peripheral blood ATL cell in origin. All these cell lines showed the same cytokine production profile, secreting IL1-alpha, IL1-beta, LD78(MIP-l alpha), TNF-alpha, IFN-gamma, and GM-CSF, but not secreting IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1 Ra), IL-4, IFN-alpha, and G-CSF irrespective of the stimulatory agents used. Such limited cytokine production may indicate the specific origin of ATL cells within the helper-inducer T cell subtypes. Moreover, these results explain some of the unusual clinical features of ATL patients.

Adult↗

PubMed1996

Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A.

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.

Aged↗

PubMed1996

[Ten-year follow-up of percutaneous transluminal coronary angioplasty].

The long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 124 patients who underwent PTCA between October 1982 and June 1985. Seventy-six patients had their proximal coronary arteries completely revascularized by PTCA (including repeat PTCA) and follow-up angiography showed the vessels were patent 3 to 6 months after the last intervention (group A). The other 48 patients showed incomplete revascularization (group B). The 10-year event-free survival rates from cardiac death and non-fatal myocardial infarction were 89.7% in group A and 93.5% in group B, respectively. Survival rates free from cardiac death, myocardial infarction, coronary bypass surgery, and repeat angioplasty for new lesions were 82.5% and 62.7%, respectively (p < 0.001). Ninety-nine percent of patients in group A and 79.5% of patients in group B were asymptomatic at the follow-up. Coronary angiography was performed in a total of 22 patients (19 patients in group A, 3 in group B). In group A, myocardial infarction occurred in one patient 8 years after PTCA. The infarct-related lesion seemed to be the same as the previous PTCA lesion. Although the other 20 PTCA lesions were all patent without progression, nine significant and new lesions were found on the coronary angiograms. Successfully revascularized vessels remained patent for over 10 years, but new lesions sometimes occur in segments other than the previously treated segment.

Aged↗