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Biomedical subjects

T Inada

Publications and source records attributed to T Inada.

At least 145 records · Page 8Linked to original sources
PubMed1994

[Successful treatment of acute promyelocytic leukemia in a pregnant woman by using all-trans retinoic acid].

A 34-year-old woman was admitted because of pancytopenia with DIC in the 28th week of pregnancy. Bone marrow aspirate demonstrated 81.2% abnormal cells which showed Auer bodies and faggot formation. Chromosomal analysis demonstrated an abnormality, t (15; 17). The patient was diagnosed as having acute promyelocytic leukemia (APL) and started to receive treatment with all-trans retinoic acid (ATRA) 70 mg/body/day per os. She had a cesarean section and gave birth to a female infant in the 29th week of pregnancy. An increase of WBC counts was observed on the 9th hospital day, then chemotherapy with anti-cancer agents was performed additionally. Complete remission was achieved on the 27th hospital day. Management of pregnant patients with APL could be improved by using ATRA instead of conventional combinations of cytotoxic agents.

Adult↗
PubMed1994

[Adult T cell leukemia with cytomegalovirus associated hemophagocytic syndrome].

A 59-year-old woman, diagnosed as adult T-cell leukemia (ATL), was admitted because of fever and disturbance of consciousness. Peripheral blood examination demonstrated leukopenia and anemia, and subsequently thrombocytopenia. Bone marrow aspiration showed the increase of mature histiocytes with hemophagocytosis and a diagnosis of hemophagocytic syndrome (HPS) was established. She died due to respiratory failure on the eighth hospital day. Autopsy histological examination revealed systemic cytomegalovirus (CMV) infection with CMV pneumonia, and also demonstrated the findings of HPS in bone marrow, lymph nodes, and spleen. This case was considered as virus associated hemophagocytic syndrome (VAHS) developed by CMV infection. CMV is one of the causative viruses of VAHS and the opportunistic infection. In the patient with ATL in the immunodeficiency state, VAHS accompanied with opportunistic infection might be one of the causes of pancytopenia.

Cytomegalovirus Infections↗
PubMed1993

Hyperthermic enhancement of cell killing by five platinum complexes in human malignant melanoma cells grown as monolayer cultures and multicellular spheroids.

The cytotoxic properties of hyperthermia combined with cis-diammine-dichroloplatinum(II) (CDDP), and recently developed platinum complexes, (Glycolato-O-O')diammineplatinum(II) (254-S), cis-1-1-cyclobutane-dicarboxylate-(R)-2-methyl-1-4-butanediammine platinum(II) (NK-121), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), and (-)-R-[2-(aminomethyl)pyrrolodine](1,1- cyclobutanedicarboxylato)-platinum(II)monohydrate (DWA-2114R) were studied in vitro in monolayer cultures and multicellular spheroids of HMV-I human malignant melanoma cells. Hyperthermia at 44 degrees C for 30 min was applied during the latter part of 1 hr drug exposure. Cell survival was compared after drug treatments in cells exposed or not exposed to heat. Cytotoxicity was assessed by clonogenic assays. In exponentially growing monolayer cultures, marked hyperthermic sensitization was observed by each of the five platinum complexes studied. The dose modifying factors obtained were almost the same in these drugs. Unlike monolayer cells, the spheroids were appreciably different with regard to hyperthermic sensitization among platinum complexes. The order of the magnitude was as follows: CDDP, DWA-2114R, 254-S, CBDCA, and NK-121. In the low dose region, however, 254-S was the most thermally sensitized. These results suggest that the microenvironment factor within spheroids may significantly affect the cytotoxicity of platinum complexes combined with hyperthermia. On the basis of these findings using spheroids, CDDP, DWA2114R, and 254-S appear to be promising platinum complexes for use with hyperthermia clinically as far as hyperthermic sensitization is concerned.

Antineoplastic Agents↗
PubMed1993

Characteristics of neutron beam generated by 500 MeV proton beam.

A neutron irradiation facility was constructed at PARMS, University of Tsukuba to produce an ultrahigh energy neutron beam with a depth dose distribution superior to an x-ray beam generated by a modern linac. This neutron beam was produced from the reaction on a thick uranium target struck by a 500 MeV proton beam from the booster synchrotron of the High Energy Physics Laboratory. The percentage depth dose of this neutron beam was nearly equivalent to that of x-rays around 20 MV and the dose rate was 15 cGy per minute. The relative biological effectiveness (RBE) of this neutron beam has been estimated using the cell inactivation effect and the HMV-I cell line. The survival curve of cells after neutron irradiation has a shoulder with n and Dq of 8 and 2.3 Gy, respectively. The RBE value at the 10(-2) survival level for the present neutron beam as compared with 137Cs gamma rays was 1.24. The results suggest that the biological effects of ultrahigh energy neutrons are not large enough to be useful, although the depth dose distribution of neutrons can be superior to that of high energy linac x-rays.

Cell Survival↗
PubMed1993

Proliferative activity of gastric cancer assessed by immunostaining for proliferating cell nuclear antigen.

The growth activity of 107 gastric carcinomas was assessed by immunohistochemical staining for formalin-fixed, paraffin-embedded tissue with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). When the tumor doubling times (Tds) of 10 patients were estimated from the serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9, there was an inverse correlation between the Tds and PCNA labeling index (LI) at P = 0.055. Flow-cytometric analysis was carried out by double staining for PCNA and DNA using fresh materials from 14 patients. The PCNA-positive cell fraction revealed by flow cytometry showed a good linear correlation with PCNA LI in routinely stained tissue. The LI of well-differentiated adenocarcinoma was significantly higher than that of the poorly differentiated type. When the LI was analyzed in well- or poorly differentiated adenocarcinoma, the value was significantly higher in the well-differentiated type with hepatic metastasis and in the poorly differentiated type with lymph node metastasis.

Adenocarcinoma↗
PubMed1993

A pharmacodynamic and pharmacokinetic study of fluoropyrimidines in a nude mouse system and in postoperative patients with gastric cancer.

To evaluate the effect of the oral fluoropyrimidines, tegafur and uracil (UFT) and 5-fluorouracil (5-FU), a pharmacodynamic analysis was conducted using a nude mouse system and patients. In the nude mouse system, UFT and 5-FU showed similar marginal effects against the human tumor xenograft Co-4, and the concentration of 5-FU in serum 1 h after the last administration being 0.04 micrograms/ml, which was assumed to be the minimum effective concentration. (MEC). Postoperative patients were subdivided into three groups, being: those who underwent subtotal gastrectomy and received UFT; those who underwent subtotal gastrectomy and received 5-FU; and those who underwent total gastrectomy and received UFT. In the UFT groups, the concentration of 5-FU in the portal and peripheral blood showed similar elimination in terms of the peak concentration (Cmax) and the area under the curve (AUC). In the 5-FU groups, the AUC and Cmax were significantly higher in portal blood than peripheral blood. The concentrations in the portal blood of the 5-FU group and in the portal and peripheral blood of the UFT group were significantly higher than the MEC (0.04 micrograms/ml). From these pharmacodynamic data, it was concluded that postoperative chemotherapy with oral fluoropyrimidines can achieve the MEC in portal and peripheral blood.

Adenocarcinoma↗
PubMed1993

Characteristics of proton beams after field shaping at PMRC.

The proton irradiation control system was developed for cancer radiotherapy at the Proton Medical Research Center, with the extension of a beam line connected to a synchrotron at the High Energy Physics Laboratory. The initial energy of the 500 MeV proton beam supplied by the accelerator is degraded down to 243 MeV after passing through a graphite rod. In the control system, a proton beam is scattered to form a large field, its Bragg peak width is spread out, and its energy is degraded to the optimum value with a range covering tumour depth. The characteristics of the devices required for these procedures have been investigated from the viewpoint of the relationship between dose rate and field flatness, taking the setting-up geometry of these devices into consideration.

Humans↗
PubMed1993

Replication of lactate dehydrogenase-elevating virus in various species cell lines infected with dual-, ampho- and xenotropic murine leukaemia viruses in vitro.

Lactate dehydrogenase-elevating virus (LDV) replicates in mouse macrophages in vivo and in vitro. It has been shown that LDV infects and replicates in motorneurons of the spinal cord of old, immunosuppressed C58 mice, which results in an acute poliomyelitis. In spite of extensive study, cells or cell lines other than macrophages which could support LDV infection and replication in vitro have not yet been detected. We have shown that LDV can replicate in mouse or rat cell lines which were previously infected with ecotropic murine leukaemia virus (MuLV). It was examined in this study whether other types of MuLV (dualtropic, amphotropic and xenotropic viruses) can also render the mouse cells or cells of other species susceptible to LDV infection as well as the ecotropic viruses. LDV infection and replication were seen in mouse cells infected with ecotropic, dual-tropic and amphotropic viruses. These were also seen in mink, rabbit and human cell lines infected with dual-, ampho- and xenotropic viruses. These results suggested that virtually all four classes of MuLV have the ability to elicit, in mouse cells or cells from heterologous species, permissiveness to LDV infection. The percent of LDV-infected cells increased up to approximately 80% in concentrated neurovirulent LDV-C-infected ecotropic MuLV-infected-mouse cells. The susceptibility of the cells gradually declined when they were maintained for more than one month. The LDV antigen-positive cells appeared as early as 6-8 h p.i., when a large amount of LDV and MuLV were added simultaneously. The replication of LDV was inhibited in MuLV-infected cells which had been treated previously with actinomycin D and cycloheximide, but not with zidovudine (AZT). A small percent of mouse cells became susceptible to LDV, when the cells were treated with iododeoxyuridine. This suggested that the induction of endogenous MuLV or part(s) of its genome from mouse chromosomes resulted in cells that were permissive to LDV.

Animals↗
PubMed1993

Clinical results of fractionated proton therapy.

PURPOSE: Preliminary results of a multi-site Phase I-II clinical trial investigating the efficacy of high-energy proton beams in a wide variety of human malignancies are reported. METHODS AND MATERIALS: Since 1983 proton radiotherapy using 250 MeV proton beams produced by a booster synchrotron of the National Laboratory for High Energy Physics has been carried out at Proton Medical Research Center, University of Tsukuba. As of September 1990, a total of 147 patients received a partial or full treatment with proton beams with curative intent; 92 patients (63%) were treated with proton beams alone and 55 patients (37%) with combined photon and proton beams. There were 91 males and the mean age was 61.8 years old. The follow-up observation period ranged from 10 to 97 months. With regard to a total tumor dose, nearly 80% of patients received 70 Gy or more and 53% received 80 Gy or more. While dose-fractionations used depended upon tumor sites, the large majority of patients received substantially high radiation doses in terms of larger total doses (> 70 Gy) and larger fraction sizes (> 2.5 Gy) than those traditionally used. This fractionation regimen has been used because of limited availability of the accelerator or a shortage of machine time (27-30 weeks/year, 3-3.5 hr/day), and also by the expectation that the superior dose distribution possible with protons will permit administration of high radiation doses without increasing morbidities. In connection with this, we have determined the target volume by setting margins around the tumor boundary as practically small as possible, ranging from 5 to 10 mm. RESULTS AND CONCLUSIONS: The current trial has been based on a site and dose searching program, hence a wide variety of tumor sites including the aerodigestive organs has been treated. So far, our judgment is that proton therapy has proven of potential advantage in treatment of the lung, esophageal, liver, uterine cervix, prostate, and head and neck malignancies; and of possible value in treatment of high-grade gliomas, and gastric, urinary bladder, and pediatric tumors.

Adolescent↗
PubMed1993

Comparison of the ability of lactate dehydrogenase-elevating virus and its virion RNA to infect murine leukemia virus-infected or -uninfected cell lines.

Lactate dehydrogenase-elevating virus (LDV) has a strict species specificity. Cells or cell lines other than a particular subset of mouse primary macrophages which can support LDV replication in vitro have not been identified. LDV induces neurological disorders in old C58 or AKR strains, in which the involvement of multiple copies of the endogenous N-tropic murine leukemia virus (MuLV) genome and the Fv-1 locus of the mouse has been implicated. Our previous studies have demonstrated that LDV could infect and replicate in cell lines of the mouse or other species in vitro when they were infected with MuLV. The significance of and the precise mechanism underlying this phenomenon, however, remain unclear. We demonstrated in this study the efficient infection and replication of the virus in vitro by inoculation of its RNA mixed with liposome. No significant difference either in the efficiency of RNA transfection or in the ability to support its replication was observed among the various species' cell lines examined. In addition, by RNA transfection the virus replicated with equal efficiency in MuLV-infected and -uninfected cells or in macrophages derived from mice irrespective of their age. In contrast, the pattern of the infection by virus particles was quite different; LDV replication was observed only in macrophages (particularly from newborn mice) and MuLV-infected cells. By using various LDV isolates, it was demonstrated that the capability of replication between neurovirulent, LDV type C, and the other avirulent strains was almost the same in mouse cell lines when their RNA was introduced into the cells. Higher infectivity of LDV-C to MuLV-infected cells may be due to its efficient incorporation of the particles into MuLV-infected cells.

3T3 Cells↗
PubMed1993

Proton radiation therapy for clivus chordoma--case report.

A 57-year-old male with clival chordoma developed severe hoarseness, dysphagia, and dysphonia 1 month after a second removal of the tumor. Magnetic resonance imaging demonstrated a mass 10 cm in diameter in the region of the middle clivus enhanced inhomogeneously by gadolinium-diethylenetriaminepentaacetic acid, and a defect in the skull base. There was evidence of compression of the anterior surface of the pons. He received proton irradiation employing a pair of parallel opposed lateral proton beams. The dose aimed at the tumor mass was 75.5 Gy, to the pharyngeal wall less than 38 Gy, and to the anterior portion of the pons less than 30 Gy. Time dose and fractionation factor was calculated at 148. Thirty-one months following treatment, he was free of clinical neurological sequelae. Proton therapy should be considered in treatment planning following initial surgical removal or for inoperable clivus chordoma.

Chordoma↗
PubMed1993

[Etoposide, doxorubicin, cisplatin and 5-FU (EAP-F) therapy of advanced gastric cancer--its antitumor effect and evaluation of quality of life].

Fourteen patients with advanced gastric cancer were treated with EAP-F therapy. The regimen was CD DP 40 mg/m2 day 1 and 6, 5-FU 600 mg/m2 day 2 and 4, leucovorin 20 mg/m2 day 2 and 4, etoposide 60 mg/m2 day 3 and 5, and doxorubicin 20 mg/m2 day 7, with repetition every 28 days. Thirteen patients were evaluable; one patient was CR, four were PR, five were NC and three were PD. The response rate was 38.5% and median survival was 7 months. Hematologic toxicities were moderate to severe but tolerable, gastrointestinal toxicities were mild and renal toxicity was absent. Quality of life (QOL) of the patients was evaluated by means of symptom-free ratio (duration of symptom-free to survival time) and outpatient ratio (duration at home in relation to survival time). Patients with lymph node metastasis showed a higher symptom-free ratio and outpatient ratio than those with liver metastasis or peritoneal dissemination. All high-QOL patients were chemotherapy responders. In conclusion, EAP-F therapy is effective for advanced gastric cancer and its side effects are tolerable. CR or PR is necessary to achieve a high QOL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Proton irradiation synchronized with respiratory cycle].

A sensitive strain gauge was used to detect the movement of the chest wall in order to synchronize an irradiation control system with the respiratory cycle. The output timing signal from the system is transferred to the proton accelerator for synchronized irradiation. The timing signal is set during the expiratory phase at a duration of 1.5 to 2 seconds. The efficacy of this method was evaluated by dose volume histogram based on the treatment planning program with CT images. The volume spared by this novel method was calculated in several cases, and results suggest that the method was highly effective.

Humans↗
PubMed1992

Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: a study in reference to thymidylate synthetase activity inhibition.

To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc x 14, and 5-FU, given as 60 mg/kg q4d x 3 ip, showed additive antitumor activity against Co-4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU.

Adenocarcinoma↗
PubMed1992

Behavioral and neurochemical effects of continuous infusion of cocaine in rats.

The ability of continuous intravenous infusion of cocaine (60 mg/kg per day for 11 or 12 days; by osmotic minipump) to alter responses to acute injection of cocaine (20 mg/kg, i.p.; given 24 hr after termination of the infusion by minipump) was tested in conscious, tethered Sprague-Dawley rats. Extracellular levels of cocaine, dopamine and metabolites of dopamine in the striatum were determined by in vivo microdialysis. Locomotor activity and stereotyped behavior were evaluated simultaneously during dialysis sampling. Prior infusion of cocaine blunted the ability of acute challenge with cocaine to increase the efflux of dopamine in the striatum, locomotor activity and stereotypy. Increases in extracellular levels of homovanillic acid in the striatum were significantly greater in cocaine-infused rats than vehicle-infused controls, both prior to and after acute injections of cocaine. However, no differences between these two groups were observed in levels of cocaine in the striatum after acute challenge. Extracellular levels of dopamine in the striatum correlated significantly (P less than 0.05) with stereotypy in both groups but with locomotor activity only in cocaine-infused rats. The results indicate that behavioral tolerance occurred after continuous intravenous infusions of cocaine, that this was correlated with neurochemical tolerance to acute cocaine challenge and that alterations in the metabolism of cocaine did not account for the observed behavioral responses.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Cocaine elevates striatal dopamine efflux in spontaneously hypertensive and Wistar-Kyoto rats.

The effects of acute cocaine administration on central dopaminergic systems were examined in the striata of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats with the use of an in vivo microdialysis technique. Increased extracellular levels of dopamine were observed for 45 to 75 minutes following acute cocaine administration in both halothane-anesthetized and conscious SHR and WKY. However, no significant differences were noted between anesthetized and conscious SHR and WKY in either baseline levels or cocaine-induced changes in extracellular levels of dopamine and its metabolites. A positive, linear correlation between extracellular levels of dopamine and cocaine was demonstrated for the 60-min period following acute cocaine administration in both SHR and WKY. The slopes of the linear regression plots obtained from the data of each 15-min sample was slightly, but significantly, higher in conscious SHR than in conscious WKY. The present results suggest a transient and dose-related stimulation of striatal dopamine release following acute cocaine administration and a linear relationship between striatal extracellular levels of dopamine and cocaine in both SHR and WKY.

3,4-Dihydroxyphenylacetic Acid↗