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Biomedical subjects

Y Okamoto

Publications and source records attributed to Y Okamoto.

At least 307 records · Page 17Linked to original sources

Hepatic arterial infusion chemotherapy combined with hyperthermia for metastatic liver tumors of colorectal cancer.

The efficacy of combined hepatic arterial infusion chemotherapy and hyperthermia for unresectable hepatic tumors of colorectal cancer was retrospectively compared with hepatic arterial infusion chemotherapy alone. Nine cases were treated with combination therapy and eight cases were treated with hepatic arterial infusion alone. The response rate in the combined hepatic arterial infusion/hyperthermia group was higher (44% v 25%) and the survival period longer (2-year survival, 35% v 12%) than in the group treated with hepatic arterial infusion alone. The toxicity was not severe, with the exception of gastrointestinal symptoms, suggesting that this combination of modalities is useful in the treatment of metastatic liver tumors.

Aged↗

[Cytokine producing ability of peripheral blood mononuclear cells in the clinical course of pulmonary tuberculosis].

Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10)-producing ability of peripheral blood plastic-dish adherent cells and non-adherent cells obtained from patients with active pulmonary tuberculosis (N = 17) and healthy controls (N = 14) upon stimulation with purified protein derivatives (PPD) were assessed. Adherent cells and non-adherent cells were obtained two times from each patient with active pulmonary tuberculosis without any underlying diseases, on admission before the initiation of administering anti-tuberculous drugs and 2 months later from the negative conversion of Mycobacterium tuberculosis in sputum culture. ELISA was performed to measure IFN-gamma and IL-10 levels in culture media of adherent cells and non-adherent cells stimulated with PPD. IFN-gamma levels produced by non-adherent cells on admission were significantly higher than that of healthy controls (p < 0.001). Elevated IFN-gamma levels on admission was reduced after treatment for tuberculosis (p < 0.03), but still remained higher than that in healthy controls. IL-10 levels of non-adherent cells of patients were lower than those of healthy controls, although the difference was not significant. IL-10 levels produced by non-adherent cells on admission correlated with the time needed for negative conversion of bacilli in sputum culture (p < 0.05). IL-10 level produced by adherent cells from nutritionally normal patients were significantly higher than that of healthy controls (p < 0.05), and elevated IL-10 level was significantly reduced after therapy (p < 0.05). In the normonourished patients, the time needed for negative conversion of the bacilli in sputum culture of patients kept higher level of IL-10 of non-adherent cells (N = 5) was significantly longer than that of patients reduced IL-10 level after therapy. These results suggest that IL-10 produced by monocytes may diminish the TH1 responses of patients with pulmonary tuberculosis.

Acute Disease↗

Transduction of retrovirus-mediated NeoR gene into CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized infant and cord blood.

To help establish an effective gene therapy protocol for patients with congenital metabolic diseases, we evaluated retrovirus-mediated transduction and long-term (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) of infant and cord blood (CB). The results were compared with those in bone marrow (BM) CD34+ cells. The final purity of the CD34+-enriched fraction from PB, CB, and BM, based on FACS analysis, was 88 +/- 14%, 73 +/- 13%, and 68 +/- 19% (mean +/- SEM), respectively. Cells were then cultured for 96 hours with supernatant containing the vector in the presence of interleukin (IL)-3, IL-6, and stem cell factor (SCF). The average efficiency of gene transfer into mobilized PB (n = 5) or CB CD34+ cells (n = 6) was significantly higher than that into BM CD34+ cells, as measured by G418-resistant colony-forming units for granulocyte/macrophage (CFU-GM; 59% or 58% vs. 39%; p < 0.05) and PCR-positive CFU-GM (83% or 79% vs. 53%; p < 0.05). When the evaluation was made in an LT culture system with irradiated allogeneic marrow stroma, these efficiencies were, respectively, 74% or 61% vs. 34% (p < 0.005 or < 0.02) for G418-resistant CFU-GM at week 5 of long-term culture, and 88% or 83% vs. 63% (p < 0.05) for PCR-positive CFU-GM. Fluorometric examination was performed for cell-cycle analysis before and after culture, and the results showed that the fraction of cycling cells was largest in freshly prepared BM (18%), whereas only a small portion of PB (4.6%) and CB (2%) was cycling. However, this value was 17% in BM, 22% in PB, and 13% in CB after culture. These results suggest that mobilized PB from small children and CB cells are suitable and realistic targets for clinical gene therapy and that tandem transduction procedures can be achieved by combining CB and PB.

Antigens, CD34↗

[A case of Mycobacterium intracellulare infection associated with sinobronchial syndrome].

The patient was 71-year-old male with a history of sinobronchial syndrome since 8 years ago. He has been suffering from cough, sputum and upper abdominal discomfort since January 1994. He was diagnosed as an early gastric cancer by endoscopy, and his chest X-ray film showed an infiltrative shadow in the right upper lung field. A smear of the sputum specimen was positive for acid fast bacilli, which were later identified as Mycobacterium intracellulare. In this case, before the Mycobacterium intracellulare infection, it was confirmed that his mucociliary transport was severely impaired by using aerosol inhalation cine-scintigraphy. This case suggests that an impairment of the local defence mechanisms may play an important role in the pathogenesis of Mycobacterium intracellulare infection.

Aged↗

[Tissue polypeptide antigen as a biological marker of malignant pleural mesothelioma].

To evaluate the role of tissue polypeptide antigen (TPA) as a biological marker of malignant pleural mesothelioma (MPM), we used immunohistochemical techniques to detect TPA in tumor cells, and we measured the content of TPA in serum from patients with MPM. In 14 of 16 patients with MPM, TPA was detected in the cytoplasm of tumor cells. Epithelial-type cells from 11 of 12 patients were stained positively (91.7%), and sarcomatous-type cells from 7 of 8 patients were stained positively (87.5%). Serum TPA levels were abnormally high in 7 of 9 patients. Two of three patients with stage-I disease had normal serum TPA levels, and all patients whose disease was at stage II or higher had abnormal serum TPA levels. Serum TPA levels increased as MPM progressed. These results suggest that the serum TPA level can be used as a biological marker of MPM.

Adult↗

[A case of local advanced cervical esophageal cancer treated with concurrent radiochemotherapy followed by surgery].

A 61-year-old-male with local advanced inoperable cervical esophageal cancer (squamous cell carcinoma, T4N1M0 stage III) was treated by concurrent radiochemotherapy. A dose of 50.6 Gy/46 Fr/36 days and one course each of CDDP-5-FU and nedaplatin-5-FU were delivered safely. Radical surgery could be performed thereafter because of the good tumor response. Pathological CR was obtained in metastatic cervical lymph nodes and almost total necrosis in primary cancer. Concurrent radiochemotherapy produced a significant improvement in this case of advanced cervical esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[The effects of premedication on induction doses of propofol and hemodynamic responses during induction].

We chose five sedatives for premedication and investigated the effect of these drugs on the induction doses of propofol. One hundred patients were allocated into one of five groups of 20. These groups consisted of control group (C) given only atropine 0.5 mg i.m.; CL group (plus clonidine 0.15 mg orally); H group (plus hydroxyzine 25 mg i.m.); M group (plus midazolam 3 mg i.m.) and D group (plus diazepam 10 mg orally). The induction dose was measured using loss of count technique. Arterial pressure and heart rate were measured, before and after propofol induction as well as after intubation. We also calculated rate pressure products (RPP) at each point. The induction doses were significantly lower in M-group than those in C-group. On the other hand, in hemodynamic responses, RPP was unchanged in any groups after propofol induction and after the intubation. Both propofol and midazolam have been known to have a depressive effect on the central nervous system via GABA-A receptor-mediated inhibition, although the exact receptor for propofol is unknown. We thought, therefore, that when the interaction occurred, both midazolam and propofol had the same effect on the GABA-A receptor and increased chloride ion flux through the channels. Hydroxyzine and clonidine, however, do not share a common receptor or exert effect on the GABA-A receptor. We consider that this was one of the reasons why induction doses of both H and CL group could not decrease significantly. We concluded that midazolam 3 mg decreased propofol induction dose significantly. Both midazolam 3 mg and clonidine 0.15 mg decreased RPP before induction and hemodynamic responses to induction and intubation were stable.

Adult↗

[Coronary circulation-derived plasma in patients with vascular restenosis stimulates the growth of coronary artery smooth muscle cells in culture].

To clarify the role of locally secreted humoral factors in coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA), we studied the effects of coronary circulation-derived plasma from patients with and without restenosis on the growth of coronary artery smooth muscle cells (CASMC) in culture. Specific coronary plasma-dependent growth stimulation/inhibition of cells (CASMC and human umbilical venous endothelial cells) was estimated by subtracting the stimulatory activity, determined by bromodeoxyuridine incorporation, of the pre-coronary plasma from that of the post-coronary plasma. Coronary-specific plasma from five patients with restenosis showed a stimulatory effect on the growth of CASMC, whereas that from four patients without restenosis showed an inhibitory effect. On the other hand, they showed the opposite effects on the growth of endothelial cells. These findings suggested that the local environment is closely associated with the development of restenosis and may play a crucial role. Analysis of coronary circulation-derived plasma may facilitate clarification of the mechanism of restenosis.

Aged↗

[The relation between diabetes mellitus and IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and monocytes in patients with pulmonary tuberculosis].

Diabetics are prone to bacterial infection in part, due to polymorphonuclear neutrophil dysfunction, but the precise mechanism is not yet fully explained. Of many complications, diabetes mellitus (DM) is one of the most common diseases, which causes pulmonary tuberculosis. To elucidate the mechanism of susceptibility to tuberculosis infection in patients with diabetes mellitus, we measured IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and autologous monocytes stimulated with live BCG in patients with pulmonary tuberculosis complicated with DM (TB + DM) or without DM (TB) and healthy controls. The levels of IFN-gamma and IL-12 production in TB patients were significantly lower than those in the control. These cytokine productions were also lower in TB + DM patients than in TB patients significantly. The level of IL-10 production in TB patients were highest among these three groups. The production of this cytokine in TB + DM patients was lowest. The level of IFN-gamma production was significantly lower in TB + DM patients under poor DM control than in those patients under good DM control and showed a significant negative correlation to HbA1c, an indicator of diabetic control. The period for negative conversion of culture finding in TB + DM patients under poor control was prolonged when compared with those in TB patients. These results demonstrated the difference in cytokines secretion profile between TB patients and TB + DM patients, and suggest that the immunological mechanism underlying pathogenesis of tuberculosis might work differently between these two patients groups.

Adult↗

[A study on the prognosis of patients with asbestos pleurisy].

We investigated the outcome of patients with asbestos pleurisy. The mean follow-up period of 12 patients was 6.5 +/- 3.7 years. Recurrence occurred in 5 patients (41.7%). Six of the cases recurred contralateral to the original lesion, while one recurred ipsilaterally. The mean period from onset to recurrence was 2.8 +/- 2.8 years. Five of the cases ended in death, and the mean period from onset to death was 5.0 +/- 3.1 years. Two patients died from pneumonia, 2 died from respiratory failure due to progressive pleural fibrosis, and 1 died from lung cancer. One of the 2 patients with progressive pleural fibrosis had leukopenia. It has been reported that the majority of cases of asbestos pleurisy resolve spontaneously, with a good prognosis. However, because of the possible mortality associated with respiratory failure caused by progressive pleural fibrosis, it seems prudent to follow patients with asbestos pleurisy closely.

Aged↗

[Radiotherapy for adenocarcinoma of the uterine cervix].

One hundred three patients with adenocarcinoma of the uterine cervix treated with radiotherapy between 1975 and 1992 were evaluated. The results for 24 patients treated with radiotherapy alone were as follows: The overall 5-year survival rates for Stages I + II (N = 12) and III + IV (N = 12) were 52% and 16%, respectively, lower than those for squamous cell carcinoma (stage I: 89%, II: 54%, III: 44%, IV: 19%). The overall response rate was 79.1%, and the recurrence rate was 54.2% (local recurrence: 29.2%, distant metastasis: 33.3%). In Stage I + II patients with an intracavitary irradiation dose of 40 Gy (LDR) or more, there was no local recurrence. In stage III + IV patients, local recurrence was recognized in spite of the high dosage of intracavitary irradiation. The results for 79 patients treated with combined irradiation and operation were as follows: The overall 5-year survival rates for Stages I, II, III and IV were 76%, 60%, 57%, and 0%, respectively. The incidence of lymph node metastasis was 30.4%, and for Stages I, II, III and IV was 26.7%, 34.6%, 28.6%, and 100%, respectively. This showed that adenocarcinoma had a higher incidence of lymph node metastasis after the early stage. The recurrence rate for patients with lymph node metastasis was 75.0%, significantly higher than 25.4% for patients without lymph node metastasis (p < 0.001). To improve prognosis, 40 Gy or more of intracavitary irradiation dose (LDR) and systemic chemotherapy to prevent distant metastasis are recommended for stage I and II cases. For stage III and IV cases, it was thought to be difficult to control local disease with radiation alone. Additional treatment should be used for these cases, i.e. intraarterial infusion, chemotherapy, hyperthermia and so on.

Adenocarcinoma↗

[The relationship between a decrease in fat mass and serum levels of TNF-alpha in patients with chronic obstructive pulmonary disease].

To investigate the relationship between malnutrition and TNF-alpha levels in patients with chronic obstructive pulmonary disease (COPD), we measured concentrations of TNF-alpha in serum from fifty four patients with stable COPD. The patients were divided into three groups, according to ideal body weight (IBW): group A, %IBW > or = 90; group B, 90 > %IBW > or = 80; group C, %IBW < 80. Serum TNF-alpha levels in group C were significantly higher than in group A (mean +/- SD; 3.00 +/- 0.43 pg/ml and 2.25 +/- 0.29 pg/ml, respectively, p < 0.0001), group B (2.41 +/- 0.47 pg/ml, p < 0.001), and healthy controls (2.33 +/- 0.30 pg/ml, p < 0.001) who were age- and %IBW-matched with patients in group C. Sixteen patients with COPD underwent body composition analysis by dual energy X-ray absorptiometry. Serum TNF-alpha levels in patients with COPD significantly correlated with fat mass (r = -0.67, p < 0.001). No association was observed between lean mass and serum TNF-alpha levels. These data suggest that TNF-alpha is involved with malnutrition in patients with COPD, and that TNF-alpha may cause a decrease in fat mass in patients with COPD.

Absorptiometry, Photon↗

[Factors affecting active-life orientation among the elderly in a community in Japan and its relationship to social activities].

We surveyed a stratified random sample of 205 person from 45,500 residents, aged 65 years or older, in a city of Japan using an interview schedule including scales of active-life orientation, social activities and other covariates. A total of 157 (77%) participated in the study. The main results were as follows: 1) Significantly higher scores of active-life orientation were observed in those who currently worked, than in those who did not work in males and females (p < 0.05). In males, scores of active-life orientation were significantly higher in those who had hobbies than in those who did not (p < 0.05); in those who traveled during the past year than in those who did not (p < 0.05). 2) In multiple linear regression analysis, PGC scale scores positively and significantly correlated with score of active orientation in males and females (p < 0.05). Age negatively correlated with the scores in males. Scores of affiliation orientation positively correlated with scores of active orientation, and satisfaction with available social support negatively correlated with the scores in females (p < 0.05).

Aged↗

[CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].

We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

Aged↗

Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses.

One of the important mechanisms of immunosuppression in the tumor-bearing status has been attributed to the down-modulation of the CD3 zeta chain and its associated signaling molecules in T cells. Thus, the mechanism of the disappearance of CD3 zeta was investigated in tumor-bearing mice (TBM). The decrease of CD3 zeta was observed both in the cell lysate and intact cells. Direct interaction of T cells with macrophages from TBM (TBM-macrophages) induced the decrease of CD3 zeta, and depletion of macrophages rapidly restored the CD3 zeta expression. We found that treatment of such macrophages with N-acetylcysteine, known as antioxidant compound, prevented the decrease of CD3 zeta. Consistent with this result, the addition of oxidative reagents such as hydrogen peroxide and diamide induced the decrease of CD3 zeta expression in T cells. Consequently, the loss of CD3 zeta resulted in suppression of the antigen-specific T-cell response. These results demonstrate that oxidative stress by macrophages in tumor-bearing status induces abnormality of the T-cell receptor complex by cell interactions with T cells. Therefore, our findings suggest that oxidative stress contributes to the regulation of the expression and function of the T-cell receptor complex.

Animals↗

Preparation of silica gel-bonded amylose through enzyme-catalyzed polymerization and chiral recognition ability of its phenylcarbamate derivative in HPLC.

Amylose was prepared by enzymatic polymerization of alpha-D-glucose 1-phosphate dipotassium catalyzed by a phosphorylase using two kinds of the primers derived from maltopentaose, and then it was chemically bonded to silica gel to be used as a chiral stationary phase (CSP) in high-performance liquid chromatography. In method I, maltopentaose was first lactonized and allowed to react with (3-aminopropyl)triethoxysilane to form an amide bond. Amylose chains with a desired chain length and a narrow molecular weight distribution were then constructed by the enzymatic polymerization. The resulting amylose bearing a trialkoxysilyl group at the terminal was allowed to react with silica gel for immobilization. In method II, maltopentaose was first oxidized to form a potassium gluconate at the reducing terminal. After the enzymatic polymerization was performed with the potassium gluconate, the amylose end was lactonized to be immobilized to 3-aminopropyl-silanized silica gel through amide bond formation. Two amylose-conjugated silica gels thus obtained were treated with a large excess of 3,5-dimethylphenyl isocyanate to convert hydroxy groups of amylose to corresponding carbamate residues. The CSP derived through method II was superior in chiral recognition to the CSP derived from method I and showed better resolving power and higher durability against solvents such as tetrahydrofuran compared with a coated-type CSP. Influences of degree of polymerization of amylose, the spacer length between amylose and silica gel, and mobile phase compositions on chiral recognition were investigated.

Amylose↗