[Combination chemotherapy with BH-AC, mitoxantrone, etoposide, and prednisolone to refractory or relapsed malignant lymphoma].
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Biomedical subjects
Publications and source records attributed to T Satoh.
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We reported two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil (5-FU), cisplatin (CDDP) and cytarabine (Ara-C), 5-FU (300-350 mg/body) was given by continuous intravenous infusion. Ara-C (20-40 mg/body) by continuous infusion and CDDP (15-20 mg/body) were added intravenously for 3-6 days. For case 1, epirubicin (30 mg/body) was also given on the first day of each therapy course. Case 1 was a 62-year-old female who had gastric cancer with liver metastasis, ovarian metastasis and peritonitis carcinomatosa. After 3 courses of the chemotherapy, reduction of ovarian metastasis greater than 75% was observed. The value of CA125 decreased from 6,800 U/ml to 527 U/ml and ascites disappeared. Case 2 was a 54-year-old male who had type 3 advanced gastric cancer with multiple liver metastases. He received 6 courses of the therapy. Both primary and metastatic tumors showed over 50% reduction in tumor size. These suggested that this combination therapy was effective for inoperable advanced gastric cancers.
CD80 (B7-1) and CD86 (B7-2/B70) have recently been identified in cultured human Langerhans cells (LCs), although their role and regulatory properties remain unclear. We present our comparison of the expression of the molecules, mRNAs and the function between CD80 and CD86 in human LCs treated by interferon gamma (IFN-gamma). We examined the regulatory properties of CD80 and CD86 expression in human LCs pretreated with IFN-gamma. Flow cytometric analysis indicated that the mean fluorescence intensity of CD86 but not CD80 was enhanced. However, the percentage modulation of both CD80 and CD86 positive cells were significantly up-regulated in a dose-dependent manner, after 48-h culturing with IFN-gamma. The regulatory properties of CD80 and CD86 mRNA expressions in human LC were studied using polymerase chain reaction methods. We found that both CD80 and CD86 mRNA of enriched LCs following IFN-gamma pretreatment for 12 h were higher than those without pretreatment. We have demonstrated that the primary allogeneic mixed epidermal cell-lymphocyte reaction induced by human LCs treated by IFN-gamma increased in a dose-dependent manner. There was a 61.5% inhibition by anti-CD86 monoclonal antibody and a 32.5% inhibition by anti-CD80 monoclonal antibody. These data indicate that the CD80 and CD86 expression of human LCs may be differently regulated by IFN-gamma.
The specific accumulation of radiolabeled anti-carcinoembryonic antigen (CEA) monoclonal antibody (MoAb) CEA 102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with [13I]-labeled intact CEA 102 or its F(ab')2. Primary tumor and liver metastases were successfully detected by external scanning with gamma camera in four cases. Autoradiographic study using FCR showed predominant localization of [13I]-labeled CEA 102 in primary tumors and liver metastases in all cases. Even the small-sized liver metastasis (0.5 cm) was clearly visualized. The pixel distribution curves showed the heterogeneity of the distribution of administered MoAb in the tumors. In the quantitative distribution analysis of CEA 102, the uptake of the primary tumor was 10-fold greater than that of the normal colon mucosa. These results suggest that MoAb has great potential in radioimmunodetection as well as possible use in antibody-directed therapy.
A 28-year-old woman with heart failure was hospitalized at 21 weeks of gestation. Nine years previously mitral regurgitation was diagnosed, and she underwent mitral valve replacement with a Carpentier-Edwards pericardial valve. Echocardiography revealed primary tissue failure of the mitral prosthesis. Emergent mitral valve replacement was performed. Normothermic high-flow high-pressure pulsatile perfusion was performed during cardiopulmonary bypass. Fetal heart rate was monitored, and it remained above 150 bpm throughout the operation. No bradycardia was observed. The degenerated prosthetic valve was replaced with another Carpentier-Edwards pericardial valve to ensure a safe pregnancy and delivery. Pregnancy was carried to term, and a healthy baby was delivered vaginally.
A polyethylene glycol treatment was given to fuse KSEK6 cells, an established cell line derived from porcine embryo kidney, with the lymphocytes, separated from spleens of 35 apparently healthy slaughtered pigs. Eight cytopathic virus strains were isolated from the lymphocytes of these pigs. Two virus strains were isolated by inoculating the spleen tissue homogenates to KSEK6 monolayer cultures. All of viruses were identified as porcine adenoviruses according to their physicochemical, serological and immunological properties. One of these virus strains was serologically proved to be independent from six serotypes of porcine adenoviruses ever known. The electrophoretic property of viral DNA of this strain was indicated to be different from those of other reference porcine adenoviruses. This means the presence of a 7th serotype in porcine adenoviruses.
We analyzed p15 and p16 gene alterations in gastric cancer. Only MKN45 showed both homozygous deletions but other cell lines and all of tumor specimens did not show any alterations. Using RT-PCR analysis, decreased or no expression of the p16 gene was found in 1 of 7 cell lines (except MKN45) (14.2%) and in 8 of 20 tumors (40%), whereas no abnormalities of p15 gene expression were found. These results suggest that the p16 gene may correlate with tumorigenesis and tumor expansion due to decrease or loss of gene products in gastric cancer.
We hypothetized that intrathecal (IT) midazolam (M) affects renal sympathetic nerve activity (RSNA) via benzodiazepine receptors (BZR) at the spinal cord. Under alpha-chloralose anesthesia, 26 rabbits underwent surgical procedures for the cannulation to femoral artery and vein for measuring blood pressure and infusing lactated Ringer solution, respectively. Intrathecal cannulation was performed at the 7th thoracic vertebral level. RSNA was recorded from the nerve raw between the renal artery and vein using a left flank incision. In the neuraxis-intact rabbits, IT administration of low dose M (0.50%) did not affect heart rate (HR), mean arterial pressure (MAP), and integrated RSNA (IRSNA). High concentration of M (0.5%) increased HR, decreased MAP and attenuated IRSNA significantly. In the sino-aortic denervated rabbits, IT administration of 0.5% M decreased MAP and IRSNA, but intravenous 0.2 flumazenil rapidly and significantly increased MAP and IRSNA. This finding suggests that the decrease in IRSNA followed by IT M derives from BZR. In conclusion, IT high concentration of M attenuated RSNA through BZR.
We examined pulmonary hemodynamics and long-term outcome in 78 consecutive patients with chronic pulmonary thromboembolism and pulmonary hypertension. These patient's ages ranged from 19 to 75 years; the mean was 51.0 +/- 13.8 years and there was no difference in sex distribution. Mean pulmonary-artery pressure (PAm) was 44 +/- 14 mmHg and total pulmonary resistance (TPR) was 1138 +/- 634 dyne.sec.cm-5. Overall five-year survival was 58.4%, but in patients whose PAm was below 30 mmHg, the outcomes were better: all of these patients survived for at least 5 years. In patients whose PAm was above 30 mmHg, no correlation was found between the outcome and the magnitude of PAm. We divided the patients into four subgroups according to their TPR: 500 dyne.sec.cm-5 (TPR, 500 > or = TPR < 1000 dyne.sec.cm-5, 1000 < or = TPR < 1500 dyne.sec.cm-5, and 1500 dyne.sec.cm-5 < or = TPR. The five-year survivals in these groups were 100%, 88.9%, 52.4%, and 40.0%, respectively. Outcome correlated with the magnitude of TPR. TPR was useful for predicting the outcome of chronic pulmonary thromboembolism.
Recent advances in telecommunication technology have been enormous. Application of this technology in public health has the potential to markedly improve global health through better surveillance and information systems. With this assumption the GHNet was established in 1994 by representatives from academia, WHO, Pan American Health Organization, the World Bank, NASA, IBM, and AT & T. The GHNet consists of seven components: 1) promotion of networking with the Internet among people in public health; 2) disease tele-monitoring; 3) distance learning system with the internet; 4) connection of non-governmental health organizations; 5) training cyberdocs who are educated in both public health and telecommunications; 6) establishment of an electronic scientific research server; and 7) a home page on the World Wide Web (WWW). In order to effectively incorporate the Internet into the field, connectivity and knowing how to use it are of critical concern. More and more facilities are connected to the Internet in Japan. However, few courses teaching how to utilize the Internet are provided for people in this field. An Internet training course for people in public health was held as joint venture of the World Health Organization (WHO) and the Global Health Network (GHNet) on October 31, 1996, at the 55th Annual Meeting of Japanese Society of Public Health. Most of the participants for the course were from local public health departments and very few had previous experience with the Internet before the course. During this course participants learned how to use e-mail, how to find health resources on the WWW, how to construct a home page, and how the Internet could be utilized to improve public health, with their computers actually hooked to the Internet. From this experience, we found that this kind of course is feasible and beneficial and hope that this course would serve as a model for training people in public health.
To clarify the changes occurring in diabetic animals in the responsiveness of the myocardium to alpha 1- and beta-adrenoceptor agonists, we examined both alpha- and beta-adrenoceptor-mediated electrophysiological and mechanical responses in the depolarized right ventricular papillary muscle of streptozotocin (STZ) induced diabetic rats and age-matched controls. Both methoxamine (10(-7)-10(-4) M) and isoproterenol (10(-9)-10(-6) M) enhanced the slow response action potential in a concentration-department manner. The amplitude and the APD50 (time required for 50% repolarization) of the methoxamine-induced slow response action potential were both markedly increased in STZ-induced diabetic rats in comparison with control rats, whereas those of the isoproterenol-induced slow response were significantly decreased. The methoxamine-induced contraction in depolarized muscle was slightly but not significantly increased in STZ-induced diabetic rats, whereas the isoproterenol-induced contractile response was significantly attenuated. The maximum number of binding sites (Bmax) for [3H]dihydroalprenolol and for [3H]prazosin were both significantly decreased in diabetic rats, compared with age-matched control rats, without any change in the affinity constants. The slow response action potential induced by methoxamine but not isoproterenol was attenuated by IAP (islet-activating factor) treatment (50 micrograms/kg, i.v. for 3 days). These results suggest that an alpha-adrenoceptor-mediated electrophysiological response is unmasked when the beta-adrenoceptor-mediated response is desensitized in the papillary muscle of STZ-induced diabetic rats.
From January 1990 to December 1995 we treated 35 patients (pts) with bone and soft tissue sarcoma with ifosfamide (IFM). Sixteen patients had measurable metastatic pulmonary lesion and 9 had primary lesion. Histology of the tumor included osteosarcoma in 13 pts, Ewing sarcoma in 5 pts, malignant fibrous histiocytoma of bone in 2 pts, synovial sarcoma in 7pts, primitive neuroectodermal tumor in 2 pts, and other in 7 pts. The IFM at the dose of 12-18g/m2 (mean 15. 4g/m2) for 5 to 8 days continuous infusion was administered to patients in each treatment course. The uroprotector, mesna, was also given concomitantly in 60-100% dose of IFM. Eighteen pts received one course of IFM treatment. Other pts received 2 to 8 courses of IFM treatment at three to four week intervals. The overall response rate was 40% (PR in 14 pts, NC in 18 pts, and PD in 3 pts). The response rate of 13 pts with osteosarcoma was 54% (PR in 7 pts) and 30% in 15 pts with soft tissue sarcoma (PR in 5 pts).
A 53-year-old male was admitted to our department with a chest tumor due to infiltration of lung cancer. Right upper lobectomy and a wide en bloc excision of the right upper chest wall were performed, including the 2nd, 3rd, 4th, and 5th ribs with upper lobectomy of right lung. The defect was replaced with three A-O metal plates, which joined both stumps of the ribs, from the third to the fifth rib. These metal plates were very useful because it was easy to bent and twist them to fit the defect in operation. And curved metal plates preserved a cone from of chest cage. Postoperative course was favourable without mechanical ventilation and wound infection.
We studied more than fifteen-years' follow-up results of cases treated with low-friction arthroplasty (LFA) for coxarthrosis with congenital hip dysplasia. Thirty-four LFAs in 32 patients (2 males and 30 females) were followed up for an average of 18.8 years (range: 15 to 23.3 years). The mean age at surgery was 53 years (range: 36 to 67 years). In three patients, 4 hips needed revision surgery due to loosening of the prostheses. At the final follow up, using Hodgkinson's criteria, type 0 demarcation of the socket appeared in 9 cases, type 1 in 5 cases, type 2 in 4 cases, type 3 in 4 cases, and type 4 in 12 cases. According to Harris' criteria, there was no sign of loosening of the stem in 16 cases, however there was a possibility of loosening in 8 cases, probability in 2 cases, and definite loosening in 8 cases. The survival rate with socket loosening as the end point was 76.5% at the 10 year follow-up, 67.6% at 15-years' follow-up, and 50.9% at 20-years' follow-up. The survival rate with stem loosening as the end point was 82.4% at 10-years' follow-up, 79.4% at 15-years' follow-up, and 63.8% at 20-years' follow-up. The survival rate with prostheses loosening either socket or stem as the end point was 64.7% at 10-years' follow-up, 55.9% at 15-years' follow-up, and 34.6% at 20-years' follow-up. The survival rate with revision surgery as the end point was 100% at 10-years' follow-up, 94% at 15-years' follow-up, and 85.1% at 20-years' follow-up.
The effects of epidural midazolam on heart rate (HR), mean arterial pressure (MAP) and the renal sympathetic nerve activity (RSNA) were examined. Under alpha-choloralose anesthesia, 31 male Japanese-white rabbits received epidural catheterization and surgical procedures for measurement of the renal sympathetic nerve activity. Epidural low (0.05%) and high (0.5%) concentrations of midazolam did not affect HR, but significantly decreased MAP and RSNA-spikes (the spike count of RSNA). Intravenous flumazenil significantly increased MAP and RSNA-spikes. These findings suggest that the decrease in RSNA-spikes induced by epidural midazolam is derived from the benzodiazepine receptor. Intramuscular midazolam (0.5%) did not affect HR, but decreased MAP and RSNA-spikes significantly. In the spinal cord dissected rabbits, epidural midazolam (0.5%) did not affect HR and MAP, but significantly attenuated RSNA-spikes. In conclusion, epidural midazolam attenuated RSNA through the benzodiazepine receptors of both the spinal and supraspinal nervous system.
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We investigated the effects of minor and major tranquilizers on ovarian and adrenal aldo-keto reductase activity towards five substrates in relation to ovulation in mature cycling rats. Nitrazepam (NZP) did not alter ovarian and adrenal weights or body weight, although ovulation was inhibited at 5 and 10 mg/kg. NZP decreased ovarian 13,14-dihydro-15-ketoprostaglandin F2 alpha (15KD-PGF2 alpha) and 4-benzoylpyridine (4BP) reducing activities. None of the doses of zopiclone (ZPC) influenced uterine and adrenal weights or body weight, but it increased ovarian weight at 10 mg/kg. No significant effects of ZPC on ovarian aldo-keto reductase activity were observed. NZP had inhibitory effects on adrenal aldo-keto reductase activity, whereas ZPC had a stimulatory effect. Chlorpromazine (CPZ) did not alter ovarian or adrenal weight, whereas the estrous cycles were abolished at 5 and 10 mg/kg. Reserpine (RSP) decreased ovarian weight and completely inhibited ovulation at 5 and 10 mg/kg, but it increased adrenal weight. Both CPZ and RSP decreased, dose dependently, ovarian aldo-keto reductase activity towards five substrates in agreement with the inhibition of ovulation. On the other hand, differences were found between the effects of CPZ and RSP on adrenal aldo-keto reductase activity. CPZ significantly increased 4BP reducing activity at 5 and 10 mg/kg, although no significant changes were observed in the other four reducing activities. RSP decreased 15KD-PGF2 alpha reducing activity in a dose-dependent manner, whereas the other four activities did not change.
It has been suggested that GTS-21 can improve the learning deficits and inhibit the neuro-degeneration in patients with Alzheimer's disease. This paper describes a reversed-phase high-performance liquid chromatographic assay with visible detection at 405 nm for determination of GTS-21 and its metabolite, 4-hydroxy-GTS-21 in rat plasma. The method uses solid-phase extraction with a Bond Elut C18 column. A quantitation limit of 1.0 ng/ml was achieved using 0.5 ml of rat plasma. In the validation study, the coefficients of variation and the relative errors of each compound were less than 10%. Also freeze-thaw and storage stability were confirmed. This method has proved to be applicable to the pharmacokinetic study of GTS-21 in rats.