Time-differential perturbed-angular-correlation study of alpha -phase and icosahedral Al-Mn-Si alloys.
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Biomedical subjects
Publications and source records attributed to Y Sakurai.
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A hybrid of the techniques of cellular adhesion chromatography and field-flow fractionation has been used for the effective separation of rat mesenteric B and T lymphocytes with nearly complete recovery of both cell species. Use of this hybrid technique also allows the relative binding strengths of cells to biomaterials and other surfaces to be rapidly and simply estimated. For the copolymer surface used here, B cells appear to bind with a force five times greater than T cells.
Four monoclonal antibodies (MoAbs) reactive with carcinoembryonic antigen (CEA) were obtained by hybridizing mouse myeloma cells (P3-X63-Ag8-U1) with spleen cells from nude mice (BALB/c, nu/nu) that had rejected transplanted human colonic adenocarcinomas Co-3 and Co-4 following intraperitoneal injection of spleen cells from immunocompetent mice (BALB/c). By solid-phase RIA with purified CEA and its related antigens, NCC-CO-413 (IgG2a, kappa) was shown to react with NCA and BGP-I as well as with CEA, whereas the reactivities of three other MoAbs, NCC-CO-308 (IgG1, kappa), -432 (IgG1 lambda), and -411 (IgG1, kappa) were limited to CEA. Immunohistochemical reactivities of these MoAbs to colonic carcinomas, granulocytes, and liver bile canaliculi on acetone-fixed paraffin-embedded sections ("AMeX" sections) confirmed the specificities of these MoAbs shown by the solid-phase RIA. By competition solid-phase RIA, the epitopes recognized by NCC-CO-308 and -432 were shown to be shared or located close to each other, whereas the other MoAbs were shown to recognize different epitopes. Thus, two epitopes specific to CEA and one shared by NCA and BGP-I as well as CEA were identified. Furthermore, reactivities of MoAbs with the two CEA-specific epitopes were easily abolished by heat denaturation or reduction of CEA, as revealed by solid-phase RIA and SDS-PAGE-immunoblotting, indicating that these two CEA-specific epitopes are based on the conformational structure of the CEA molecule.
The responses of 14 lines of human lung cancer xenografts in BALB/c-nu/nu mice to eight known antitumor agents were investigated. These xenografts consisted of four small-cell carcinomas (SCLC) and ten non-small-cell carcinomas (four large cell, three squamous cell, and three adenocarcinomas; NSCLC). The doses used in the experiments were the maximum tolerated dose (MTD) in nude mice and the "rational dose" (RD), the latter considered to be pharmacokinetically equivalent to the clinical dose. When given at MTDs, all drugs except 5-fluorouracil (5-FU) and methotrexate (MTX) were extremely effective against NSCLC as well as SCLC. The response rates of drug-sensitive SCLC to mitomycin C (MMC), ACNU, and vinblastine (VLB) were 100%, and those to Adriamycin (ADR) and vincristine (VCR) were 75%. In addition, the response rates of even drug-resistant NSCLC to MMC and VLB were 70% and 90%, respectively. In contrast, the response rates of NSCLC to RDs of the drugs were reduced to less than 40% and corresponded well to the respective clinical rates. In SCLC, a good correlation of experimental and clinical response rates was observed with four drugs [cyclophosphamide (CPM), ACNU, VLB, and 5-FU]. As a result, we emphasize that a more reasonable prediction of the clinical effectiveness of antitumor agents can be made by a protocol using clinically equivalent doses.
To investigate the mechanisms involved in lymphocyte adsorption on poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymer, which is utilized as an adsorbent for cell separation, the role of cellular metabolism in lymphocyte adsorption on these copolymers was evaluated. We examined the effect of lowering environmental temperature and of the drug cytochalasin B that inhibits reorganization of microfilaments in cellular cytoskeletons on lymphocyte adsorption. Although the adsorption of lymphocytes on poly(2-hydroxyethyl methacrylate) was considerably reduced in the presence of cytochalasin B or by lowering temperature, no marked influence of these factors was observed for lymphocyte adsorption on poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymers. These results suggest that, in contrast to common plastics surfaces including poly(2-hydroxyethyl methacrylate), the surface of poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymers does not stimulate or activate adsorbed lymphocytes.
Direct measurement of cytoplasmic free Ca2+ concentration in rabbit platelets in contact with polystyrene latexes was examined by monitoring an intracellular trapped fluorescent indicator dye, Fura 2, as a quantitative evaluation of platelet activation on material surfaces. It was found that an increase in cytoplasmic free calcium levels in platelets in contacting latexes was strongly reduced by the adsorption of albumin on the latex surfaces. Further, such an elevation of cytoplasmic free calcium levels was found to require a calcium influx from an extracellular medium across the platelet-plasma membrane.
Poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymers were developed for column adsorbents for separating lymphocyte subpopulations collected from rat mesenteric lymph nodes. Bead-shaped adsorbents were prepared by coating poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymer on glass beads. Separation features of the column packed with poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymer-coated glass beads were evaluated under various operating conditions. Separation efficacy, AB/AT, was significantly affected by the infusion rate of lymphocyte suspension into the column, increasing with decreasing infusion rate. T cell purity in the column effluent was almost 95% at the infusion rate of 0.1 ml/min. The infusion rate was also found to affect the detachment of adsorbed lymphocytes from the poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymer surface by mechanical pipetting; lymphocytes adsorbed at a low infusion rate were able to be detached quantitatively by suspending the lymphocyte-adsorbed beads with gentle pipetting. The detached lymphocytes thus obtained were confirmed to be enriched in B cells 1.4 times the initial mixture of B and T cells. The addition of albumin in the medium was found to affect the processes of adsorption and recovery of lymphocyte.
Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane) platinum (II) (l-OHP), was studied. This water-soluble platinum complex showed a more prominent life-prolonging effect on a mouse leukemia L1210 than cisplatin (DDP). By an intermittent treatment schedule cured mice were observed at the optimal dose. In addition, a subline of L1210 having a 40-fold resistance to DDP (L1210/DDP) showed lack of cross-resistance to l-OHP both in vivo and in vitro. Especially in vivo l-OHP was more active against L1210/DDP than against the original L1210, and all mice were cured at doses of 6.25 and 3.12 mg/kg. l-OHP was also effective against several mouse tumors such as P388 leukemia, B16 melanoma, Lewis lung carcinoma, colon 26 and colon 38 adenocarcinomas, and M5076 fibrosarcoma, though its antitumor spectrum was somewhat different from that of DDP. The synthesis of both DNA and RNA in L1210 cells was inhibited by about 50% with exposure to 10 microM of l-OHP for 1 h, followed by postincubation in drug-free medium for 6-24 h, while only the inhibition of DNA synthesis was observed by DDP in the same experiment. If severe toxicity is not observed in preclinical study, l-OHP expected to be a new clinically active Pt complex.
Changes in cerebral blood flow (CBF) and regional cerebral blood flow (rCBF) throughout the entire age range including childhood were reported. The CBF in grey matter of children was markedly higher than that found in adults and showed a negative correlation with age. In contrast, the blood flow in white matter did not show a notable decrease with age. The regional distribution of CBF in children did not exhibit the frontal lobe dominance typical of adults. The rCBF pattern began to approach that of adults with growth and by 10 yr the rCBF pattern of children was similar to that of adults.
The levels and character of carcinoembryonic antigen (CEA) in feces were investigated by sandwich radioimmunometric assay using anti-CEA monoclonal antibodies NCC-CO-411 and NCC-CO-432. Mean CEA concentration was significantly higher (P less than 0.001) in the feces from patients with colorectal carcinoma and other gastrointestinal disorders as compared to normal adults. More than 90% of the fecal CEA was trapped by a 0.22 micron membrane filter and solubilized by treatment with 1% Triton X-100 or phosphatidyl-inositol specific phospholipase C. In hydrophobic chromatography, most of the fecal CEA was eluted at the lowest (NH4)2SO4 concentration while serum CEA appeared in the more hydrophilic fractions. These results suggest that the majority of CEA exists in feces as an amphiphilic molecule or a membrane-bound form. The increase of fecal CEA may reflect the destruction and abrasion of epithelial cells in various gastrointestinal disorders.
The reactivity of antigens of 4 mouse and 3 rat derived Mycoplasma pulmonis strains to 20 naturally infected rat sera was studied. The optical density values of the same serum by enzyme-linked immunosorbent assay using the 7 strains as the antigen revealed no marked difference among the strains. M. pulmonis antigens recognized by the antibodies were analyzed by the Western immunoblot method. The antigens with molecular weights of 92 K, 66 K, and 58 K were recognized in the 7 strains at a high frequency.
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Poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymers (HA copolymers) of varying composition and chain length of the polyamine graft were prepared by radical copolymerization of 2-hydroxyethyl methacrylate with a given quantity of polyamine macromonomer having a controlled molecular weight, and their interaction with lymphocyte subpopulations (B and T cells) was estimated using a column method. From these results, it was revealed that the most suitable molecular structure of HA copolymers for separating lymphocyte subpopulations is that of an HA copolymer with 13 wt% of polyamine graft with a chain length 3000-6600 in molecular weight. It is concluded that the retention process of lymphocytes on the HA graft copolymers is driven primarily by ionic interactions between the protonated amino groups and the cells. However, the mode of the polyamine microdomain structure, that is the distribution of protonated amino groups, and the conformation of the polyamine chains, which varies with the chain length of the HA copolymer, are also important factors in determining differential lymphocyte retention.
The expression of Mycoplasma pulmonis antigen in Escherichia coli was investigated by cloning genomic DNA derived from M. pulmonis m 53, and the DNA fragment participating in antigen expression was identified. When the DNA library of M. pulmonis was screened by colony immunoassay using anti-M. pulmonis serum, 10 recombinant clones expressing seroreactive antigens were obtained. The recombinant plasmids isolated from these clones included 3.7-6.5 kilobase pair (kbp) DNA inserts, while all clones contained a common 2.3-kbp DNA fragment. Subcloning of initial DNA inserts showed that the common 2.3-kbp fragment is essential for antigen expression. Moreover, antiserum against the recombinant antigen generated from the 2.3-kbp DNA fragment recognized a native M. pulmonis antigen. The reactivity of this antiserum was absorbed specifically with M. pulmonis. These results suggest that the cloned 2.3-kbp DNA fragment codes an antigen specific to M. pulmonis.
Mycoplasma pulmonis was specifically detected by using a 2.3 kilobase pair (kbp) cloned DNA fragment derived from M. pulmonis m 53 as a probe. This probe recognized 2.3-kbp DNA fragments of three M. pulmonis strains in Southern hybridization, while it did not hybridize with the DNA of M. arthritidis or M. neurolyticum. Determination of the sensitivity of the probe by dot hybridization revealed that 10 ng of M. pulmonis DNA was detected by a biotinylated probe and 1 ng of M. pulmonis DNA was detected by a radioactive probe.
The presence of hypoxic Zone in clinical brain tumor is verified. The value of intratumoral PO2 is about 16 mmHg under the condition with physiological PaO2. Perfluorocarbon, which can transport rich O2, was used to increase intratumoral PO2. Intratumoral PO2 increased to about 36 mmHg by using Perfluorocarbon with inhalation of O2. I conducted new Protocol, namely, irradiation method should be selected altered dose fractionation when hypoxic cell of the tumor change to normoxic cell. Perfluorocarbon was administered on the day when irradiation dose is high. Clinical result showed much better than previous our result, especially in the group of glioblastoma, the mean survival duration prolonged 8 months to 2 years.
A nine-day-old female with cerebellar medulloblastoma treated by surgical and radiation therapy is reported. She suffered from vomiting within a few days after birth. Subsequently, her head became enlarged and she was admitted to our hospital. CT scan on admission showed a large mass lesion at the cerebellum expanding to the pineal portion, and marked hydrocephalus. At the age of 14 days, a ventriculo-peritoneal shunt was carried out, and at the age of 67 days, radical resection of the tumor was performed. The histopathological diagnosis was medulloblastoma. Postoperatively, radiation therapy of the brain was carried out. Irradiated dose was 30 Gy on the whole brain and 20 Gy at the location of the lesion. She was discharged at the age of seven months. She remained in good condition with no neurological deficit except for nystagmus. One week later, it was found that she was unable to move her legs and she was readmitted to our hospital. CT scan showed no remarkable change in the intracranial region, but spinal cord swelling was revealed at the Th12-L5 level. Myelography showed a filling defect at the L3-5 level. Radiation therapy of the spinal cord was performed, and the paraparesis gradually improved. However, her general condition was getting worse, and the following CT scan showed intracranial recurrence of the tumor. She deteriorated day by day and at the age of 9.3 months she expired. Brain tumors during the neonatal period are very rare, especially neonatal medulloblastoma. Only 24 cases can be found in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)