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Biomedical subjects

A Uchiyama

Publications and source records attributed to A Uchiyama.

At least 91 records · Page 5Linked to original sources

OK-432-induced enhancement of ICAM-1 expression on tumor cells positively correlates to therapeutic effects for malignant effusion.

The intracavitary injection of OK-432 has been shown to be an effective immunotherapy for patients with malignant effusion. We investigated the contribution of intercellular adhesion molecule-1 (ICAM-1) on the surface of tumor cells to its therapeutic effect. We treated 13 patients with malignant effusion with OK-432. Tumor cells were freshly isolated from effusion samples obtained before and 24 hr after initiation of the therapy. Surface expression of ICAM-1 was analyzed by flow cytometry and its relation to the therapeutic effect was analyzed. An objective clinical response was observed in 7 (53.8%) of 13 patients. Following OK-432 injection, ICAM-1 levels showed an average of 5.73-fold increase in clinical responders (7 patients), whereas no increase in nonresponders (6 patients). ICAM-1 expression more than doubled after therapy in 7 patients, 6 of whom showed a clinical response. Survival was significantly prolonged in these patients compared with that in the 6 patients in whom ICAM-1 levels did not double after therapy. Only 1 of the 6 patients in whom ICAM-1 levels did not double showed a clinical response. Pretherapeutic ICAM-1 expression was not significantly correlated with the subsequent clinical effect. OK-432 injection was associated with an increase in surface expression of ICAM-1 on tumor cells. This increased ICAM-1 expression was positively correlated with therapeutic effect, suggesting that ICAM-1 expression on tumor cells may be a useful marker for evaluation of efficacy of OK-432 therapy.

Aged↗

Characterization and augmentation of CD4+ cytotoxic T cell lines against melanoma.

Cytotoxic T cells have been implicated in the control of the progression of human melanoma. Most studies on human tumor T cell immunity have focused on the CD3+CD8+ cytotoxic T lymphocyte (CTL) phenotype; however, CD3+CD4+ CTL are important effector cells in other diseases and may also contribute to antimelanoma immunity. In this study we compared the functional activity of CD3+CD4+ and CD3+CD8+ CTL lines generated against autologous melanoma cells. CD8+ CTL had twofold higher cytotoxicity and serine esterase activity than CD4+ CTL. CD8+ CTL also were better binders to autologous melanoma cells. Binding of both CD4+ and CD8+ CTL to melanoma cells was significantly inhibited by ICAM-1 mAb. Interleukin-2 (IL-2) and IL-4 secretion was induced in both CD4+ and CD8+ CTL after stimulation by melanoma cells. A reverse transcriptase polymerase chain reaction performed on specific messenger RNA showed that both CD4+ and CD8+ CTL expressed IL-1, IL-2 and IL-4; CD4+ CTL also expressed interferon gamma (IFN). Both CTL phenotypes expressed receptors for IL-2 and IFN but only CD4+ CTL expressed the receptor for IL-4. Methods to augment CD4+ CTL growth were assessed using different combinations of cytokines. The combination of IL-2, IL-4 and IFN provided the optimal stimulation. Treatment of melanoma target cells with IL-4 and IFN enhanced CD4+ CTL recognition activity. CD4+ T cells are associated with antigen memory response and helper function, therefore activation of CD4+ CTL may be more beneficial with respect to long-term protective antimelanoma immunity.

Base Sequence↗

Neonatal assessment using the Apgar fuzzy expert system.

We applied fuzzy theory to the Apgar scoring system (APG) to devise an Apgar fuzzy expert system (AFES). Three AFESs were determined separately by each one of three doctor groups (four inexperienced obstetricians, four experienced obstetricians and four expert neonatologists) in order to demonstrate that the AFES reflected the examiner's expertise and situation. Two-hundred and sixty-seven neonates were assessed 1 min after birth by an experienced obstetrician using the APG and the three AFESs. Statistical analysis of the relationship between the APG and the three AFESs in the acidosis group showed that the AFES determined by four expert neonatologists had the highest sensitivity and were significantly different (p < 0.05) from the APG. The AFES determined by the four expert neonatologists was revealed to be a valuable tool.

Acidosis↗

Low dose intrathecal morphine and pain relief following caesarean section.

Healthy women who underwent caesarean section under spinal anaesthesia were studied to determine the extent of postoperative analgesia and side-effects produced by low doses of intrathecal morphine. Patients were randomly allocated to receive, in double-blind fashion, 0 mg (group 1: control group), 0.05 mg (group 2), 0.1 mg (group 3), or 0.2 mg (group 4) of morphine, with 10 mg tetracaine in 10% dextrose 2.5 ml. (n = 20 x 4 groups). The effect of intrathecal morphine was examined in terms of the duration until the first supplemental analgesic was needed and the numbers of the doses within the first postoperative 48 h. Pain relief was significantly greater in groups 3 and 4 than in group 1. The incidence of nausea, vomiting and pruritus increased in a dose-dependent manner. No patient developed respiratory depression. Our results suggest that postoperative analgesia lasts more than 24 h with 0.1 mg or 0.2 mg of intrathecal morphine. Since the incidence of side-effects was higher at 0.2 mg, 0.1 mg may be the optimum dose for caesarean section.

Journal Article↗

Comparative evaluation of diaphragmatic activity during pressure support ventilation and intermittent mandatory ventilation in animal model.

The aim of the present study is a comparative evaluation of the effects of pressure support ventilation (PSV) and intermittent mandatory ventilation (IMV) on diaphragmatic activity in rabbit model of neonate. The animals were divided into a PSV group and an IMV group. In the IMV group, spontaneous breathing and four kinds of IMV rate (5, 10, 15, and 20/min) were applied (Ventilator: Bear BP200, peak inspiratory pressure [PIP]: 12 cm H2O, inspiratory time: 0.6 s). In the PSV group, spontaneous breathing and four levels of PSV (3, 6, 9, and 12 cm H2O) were applied (Ventilator: VIP Bird, flow triggering). Airway pressure (Paw), flow (V), esophageal pressure (Pes), integrated diaphragmatic electromyogram (Edi), and arterial gas data were measured. Amplitudes of Pes and Edi were expressed as percentages (% Edi and % Pes) of the control value during spontaneous breathing to evaluate diaphragmatic activity. Lower IMV rates did not reduce diaphragmatic activity. Approximately half of diaphragmatic activity of control remained even at IMV 15/min. Diaphragmatic activity disappeared at IMV20/min. In contrast, PSV reduced Edi and Pes linearly according to support level. In conclusion, diaphragmatic activity could be reduced more gradually with PSV than IMV by altering ventilatory support level.

Animals↗

Transfection of interleukin 2 gene into human melanoma cells augments cellular immune response.

A preclinical model was used to determine if transfection of the interleukin 2 (IL-2) gene into human melanoma cells would augment the response of autologous and allogeneic peripheral blood lymphocytes (PBLs) from melanoma patients. IL-2 gene was transfected into three human melanoma cell lines; secretion of IL-2 from stable transfected cells was confirmed by enzyme-linked immunosorbent assay. The PBL response to these melanoma cells was then examined in a mixed-lymphocyte tumor reaction using PBLs from eight melanoma patients. The PBL response to autologous (P < 0.01) or human leukocyte antigen A cross-reactive (P < 0.05) transfected melanoma cells was significantly higher than it was to nontransfected melanoma cells. These data suggest that IL-2 gene transfection may be an important strategic approach to enhancing specific immune responses induced by a polyvalent melanoma cell vaccine.

Base Sequence↗

Postoperative recovery of arterial oxygen saturation determined by pulse oximetry in pediatric patients.

Small children are physiologically subject to arterial oxygen desaturation. However, few reports have referred to the risk factors related to postanesthetic hypoxemia and the duration of hypoxemia. The purpose of this study was to clarify these two aspects. Eighty-five ASA physical status I infants and children were included in the study. They were scheduled for minor surgery. Fifty-six underwent oral endotracheal intubation, and 29 patients breathed from a mask. Anesthesia was maintained with Enflurane or Halothane and nitrous oxide. Arterial oxygen saturation was measured with a pulse oximeter. The measurements were started shortly after patients' arrival in the recovery room, and conducted every 5 min at least for 1 hour. Ten patients had SpO2 values of less than 95%. In all except one, SpO2 decreased within 10 min after arrival in the recovery room. Age, height, and weight of these 10 children were significantly different from the remaining 75, but there were no significant differences in anesthetic duration and postanesthetic awakefulness between the group with postanesthetic hypoxemia and the one without. The importance of monitoring the clinical condition of pediatric patients after general anesthesia is universally acknowledged. Monitoring with the pulse oximeter has proven very useful and shows that, unless oxygen saturation is monitored, all children should receive supplemental oxygen.

Journal Article↗

Suppression by interferon-gamma of tumor cell-induced increase in mesothelial permeability.

The effect of interferon-gamma (IFN-gamma) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-gamma. The effect of IFN-gamma was observed when either the conditioned medium of tumor cells alone or the IFN-gamma-resistant tumor cells, K-562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-gamma. In contrast, IFN-alpha did not suppress tumor-induced mesothelial permeability. These results suggest that IFN-gamma has the potential to protect the human mesothelial cell layers against tumor cells.

Cell Communication↗

A 60-kDa phosphorylated protein from fetal human bone.

A phosphorylated protein was isolated and purified from fetal human bone. Fetal and adult human bones were decalcified with EDTA, and the extract from the fetal bone was fractionated using Q-Sepharose anion exchange chromatography. The fraction containing Ser(P) was purified by Sephacryl S-200 molecular sieving and C4 reverse-phase HPLC. The purified protein had a molecular weight of 60000 on SDS-PAGE, where the protein was stained with Rhodamine-B. The amino acid composition of this protein was different from any other reported phosphorylated proteins in human bone. However, this phosphorylated protein was difficult to detect in the adult bone extract on SDS-PAGE.

Adult↗

Fluorophores from aging human articular cartilage.

Human articular cartilages of various ages were digested with collagenase, and the fluorescence of the digests was measured as a function of age. At acidic pH, all collagenase-treated fractions were found to contain two main fluorophores with fluorescence maxima at 395 and 385 nm (excitation at 295 and 335 nm, respectively). Each fluorophore was isolated from the hydrolysate and its structure was deduced from spectral and chemical data. The 395/295 nm fluorophore was identified as pyridinoline, which is one of the non-reducible cross-linkages in collagen. The 385/335 nm fluorophore was identical to pentosidine, which was isolated from human dura mater and characterized by Sell and Monnier in 1989. Our results showed that the amount of pentosidine per collagen in human articular cartilage increases linearly with age (r = 0.929, p less than 0.005), while the amount of pyridinoline per collagen remained constant and was not correlated with age (r = 0.20). On the other hand, the amount of pentosidine per pyridinoline increased exponentially during life (r2 = 0.839, p less than 0.05).

Adult↗

Evidence that induction and regulation of lymphokine-activated killer (LAK) activity are mediated by changes in tumour-binding potential of lymphocytes after activation by interleukin-2 (IL-2).

The changes in the tumour-binding potential of human peripheral blood lymphocytes (PBL) after activation by interleukin-2 (IL-2) was investigated by directly counting the number of lymphocytes bound to lined hepatoma cell monolayers. A significant increase in the tumour-binding potential of PBL was found after activation by more than 100 U/ml of IL-2. Maximal tumour-binding potential was achieved at 1000 U/ml of activation, and an overdose of IL-2 activation slightly decreased this potential. These changes were almost exactly the same as the changes in anti-tumour cytotoxicity as measured by a 4-hr 51Cr-release assay. In addition, the kinetics of tumour binding by lymphokine-activated killer (LAK) cells was shown to be almost identical to that of tumour cell lysis. These results thus provide evidence that induction and regulation of LAK activity are mediated by changes in tumour-binding potential of lymphocytes after activation by IL-2.

Animals↗

[Eighteen-year experience of cancer immunotherapies--evaluation of their therapeutic benefits and future].

The purpose of this study is to evaluate the therapeutic benefits of cancer immunotherapies and to predict the future of these therapies. The results of our clinical trials are as follows; (1) A group of gastric and colonic cancer patients at stages III-IV treated with BCG immunotherapy showed a significant prolongation of survival period (2) A significant prolongation of the disease-free period and the survival time were observed in the PSK-treated group in a randomized clinical trial on patients with curative surgical operation for stages III-IV colonic cancer. (3) We established clinically that intracavital administration of OK-432 is a useful therapy for patients with malignant pleuro-peritoneal effusions. We found that the reduction and disappearance of effusions were observed in more than 60% of patients with this therapy and they survived significantly longer. These results indicate that the immunotherapies may be effective to prolong survival period of advanced cancer patients with improvement of their quality of life. Furthermore, a series of our studies on the intracavital OK-432 injections for malignant ascites are useful to understand the reaction of host immune system against tumor cells.

Humans↗

[Anesthesia for cesarean section in patients with fetal anomaly].

Twenty-two cases of Cesarean section due to fetal anomaly diagnosed prenatally were reviewed in terms of the anesthetic managements. In 6 cases, diazepam 0.3 mg.kg-1, which provides fetal anesthesia for surgery scheduled immediately after birth, was administered intravenously to the mothers with/without fentanyl (2 general anesthesia and 4 regional anesthesia). The diagnosis of their fetuses was congenital diaphragmatic hernia, congenital cystic adenomatoid malformation of the lung, gastroschisis or omphalocele. No fetal anesthesia was performed in the other 16 cases (15 spinal anesthesia and 1 general anesthesia). Seven of their fetuses were diagnosed as hydrops. Since the general condition of the diseased newborn is known to be deteriorated after receiving various stress and aerophagia, fetal anesthesia in Cesarean delivery has the advantage of stress reduction and prevention of aerophagia. When the newborn is considered to need immediate neonatal resuscitation or intensive care including surgery, fetal anesthesia may be a choice of anesthetic technique.

Anesthesia, Obstetrical↗