Derivation of nondiagonal effective dielectric-permeability tensors for magnetized granular composites.
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Biomedical subjects
Publications and source records attributed to M Abe.
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PURPOSE: To investigate the variation of reoxygenation patterns after single irradiation in murine tumors of different types and sizes. METHODS AND MATERIALS: Whole-body single irradiation of 13 to 15 Gy was delivered to 10 mm RIF1 tumors of C3H/He mice, 22 mm SCCVII tumors of C3H/He mice, and 16 mm EMT6 tumors of Balb/c mice. Thereafter, changes in the hypoxic fraction with time were determined by the paired survival curve method. The data were compared with the results we had ++previously obtained with 10 mm SCCVII and 10 mm EMT6 tumors. RESULTS: The hypoxic fraction at 1 h after the priming irradiation was 26% for 10 mm RIF1 tumors, 48% for 10 mm SCCVII tumors, and 100% for 10 mm EMT6 tumors. Thus, RIF1 and SCCVII tumors, both of which have few necrotic areas, showed rapid reoxygenation, whereas EMT6 tumors, which have large necrotic areas, reoxygenated slowly. Although the hypoxic fraction returned to the pretreatment level within 72 h in 10 mm SCCVII and 10 mm EMT6 tumors, it did not in 10 mm RIF1 tumors. In contrast, the patterns of reoxygenation were similar between 22 mm and 10 mm SCCVII tumors and between 16 mm and 10 mm EMT6 tumors. CONCLUSION: The three tumors showed different patterns of reoxygenation. Tumors that have a low proportion of necrosis may reoxygenate rapidly. However, tumor size appeared to have less influence on the pattern of reoxygenation.
Thiaminase I (EC 2.5.1.2) catalyzes the replacement of the thiazole moiety of thiamin with a wide variety of nucleophiles. Here we report the sequencing of a thiaminase I clone from Bacillus thiaminolyticus, the overexpression of the cloned gene in Escherichia coli, and the purification and characterization of the enzyme. Recombinant thiaminase I functions as a monomer with a Km for thiamin of 3.7 +/- 0.6 microM and a kcat of 34 s-1. Electrospray ionization Fourier-transform mass spectrometry identified a single sequencing error and demonstrated heterogeneity, finding molecular weights of 42,127, 42,198, and 42,255 due to added Ala and Gly-Ala at the amino terminus. Similar analysis of the 4-amino-2-methyl-6-chloropyrimidine inactivated enzyme indicated that the active site nucleophile involved in catalysis of the substitution reaction is located between Pro79 and Thr177. Subsequent cysteine-specific labeling and site-directed mutagenesis identified Cys113 as the active site nucleophile.
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PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.
The clinicopathological features, the immunophenotype, and the presence of Epstein-Barr virus (EBV)-associated genomes and gene products were examined in 17 cases of CD30+ anaplastic large cell lymphoma (ALCL) of B-cell type. Microscopically, the 17 cases were divided into ten cases of the monomorphic type and seven cases of the pleomorphic type. EBV was detected in 6 of 17 cases (38 per cent) by RNA in situ hybridization (ISH) with EBV-encoded RNA (EBER1). EBER1+ cases consisted of two cases (20 per cent) of the monomorphic type and four cases (57 per cent) of the pleomorphic type. The five EBER1+ cases showed clonality of the EBV genome by Southern blotting, consistent with the presence of EBV in a monoclonal proliferation. The EBV-encoded latent membrane protein 1 (LMP1) was found in all six EBER1+ cases and EBV-encoded nuclear antigen 2 (EBNA2) was present in two cases by immunohistochemistry. No expression of LMP1 or EBNA2 was observed in the EBER1-cases. The EBER1+ cases had a tendency for a more favourable prognosis than the EBER1-cases. It is concluded that EBV has an association with CD30+ ALCL of B-cell type in the Japanese population studied, and especially with the large pleomorphic type. EBV infection may play a pathoaetiological role and may influence clinical behaviour.
The nucleotide sequence of cosmid clone 9765, which contains 30.8 kb of the right arm of chromosome VI, was determined. Both strands were sequenced, with an average redundancy of 8.17 per base pair by both dye primer and dye terminator cycle sequencing methods. The G+C content of the sequence was found to be 40.3%. Fifteen open reading frames (ORFs) greater than 100 amino acids and one tRNA-Tyr gene (SUP6) were detected. Seven of the ORFs were found to encode previously identified genes (HIS2, CDC14, MET10, SMC2, QCR6, PH04 and CDC26). One ORF, 9765orfF010, was found to encode a new member of the Snf2/Rad54 helicase family. Three ORFs (9765orfR002, 9765orfR011 and 9765orfR013) were found to be homologous with Schizosaccharomyces pombe polyadenylate binding protein, Escherichia coli hypothetical 38.1-kDa protein in the BCR 5' region, and transcription regulatory protein Swi3, respectively.
The coordinate induction of protease activities and cell migration is a principal feature of endothelial cells (ECs) invading the interstitial space in the initial step of angiogenesis. However, the molecular mechanisms of these events are not fully characterized. Ets-1 is a member of the ets gene family of transcription factors, which binds to the Ets binding motif in the cis-acting elements and regulates the expression of certain genes. Four typical angiogenic growth factors, aFGF, bFGF, VEGF, and EGF, induced the expression of ets-1 mRNA in either human umbilical vein endothelial cells (HUVECs), ECV-304 cells (immortalized HUVECs), or human omental microvascular endothelial cells (HOMECs). The expression of ets-1 reached its maximum at 2 hr after factor addition and then decreased to the basal level by 12 hr. For characterization of the role of Ets-1 in angiogenesis, ets-1 antisense and sense oligodeoxynucleotides (ODNs) were constructed. The ets-1 antisense ODN but not sense ODN efficiently blocked the synthesis of Ets-1 protein by human ECs in response to angiogenic growth factors. Moreover, the ets-1 antisense ODN but not sense ODN almost completely abolished the binding of endothelial cell extract to DNA containing the Ets binding motif. The expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of ECs in response to growth factors were significantly inhibited by ets-1 antisense ODN but not by sense ODN. Tube formation by HOMECs in type 1 collagen gel stimulated with EGF was abrogated by ets-1 antisense ODN. Finally, the expression of Ets-1 protein in ECs during angiogenesis in vivo was confirmed by an immunohistochemical analysis using a murine angiogenesis model. These results indicate that the induction of ets-1 mRNA is a mutual phenomenon in ECs stimulated with angiogenic growth factors. Ets-1 appears to play an important role in angiogenesis, regulating the expression of proteases and the migration of ECs.
B1 cells usually show preferential responses to T cell-independent antigens. To ask whether B1 cells could respond to CD40-mediated stimulation for proliferation and differentiation, and whether CD40-mediated signals are involved in the production of autoantibodies by B1 cells, we compared responses to our newly established agonistic anti-mouse CD40 monoclonal antibody (mAb) between B1 and B2 cells from autoimmune-prone (NZB x NZW) F1 mice. Stimulation with this mAb induced a similar level of proliferative responses of both B1 and B2 cells, as well as an increase in expression of cell surface molecules I-A, CD54, CD23, CD80, and CD86. While co-stimulation with interleukin (IL)-4 markedly augmented proliferative as well as IgG1 and IgE antibody responses of both B and B2 cells, co-stimulation with IL-5 augmented proliferative and IgM antibody responses of only B1 cells. Splenic B1, but not B2 cells from young (NZB x NZW) F1 mice spontaneously produced substantial amounts of IgM including IgM anti-DNA antibodies, and the levels increased in case of stimulation with anti-CD40 mAb alone, or to a greater extent with the mAb plus IL-4 and IL-5. Collectively, these results indicate that splenic B1 cells from autoimmune (NZB x NZW) F1 mice have a comparable responsiveness to the CD40-mediated stimulation to that of B2 cells, which would be a potent regulatory mechanism involved in the spontaneous production of autoantibodies by B1 cells.
Corn cystatin (CC), a phytocystatin, shows a wide inhibitory spectrum against various cysteine proteinases. We produced transgenic rice plants by introducing CC cDNA under CaMV 35S promoter as a first step to obtain a rice plant with insecticidal activity. This attempt was based on the observation that many insect pests, especially Coleoptera, have cysteine proteinases, probably digestive enzymes, and also that oryzacystatin, an intrinsic rice cystatin, shows a narrow inhibition spectrum and is present in ordinary rice seeds in insufficient amounts to inhibit the cysteine proteinases of rice insect pests. The transgenic rice plants generated contained high levels of CC mRNA and CC protein in both seeds and leaves, the CC protein content of the seed reaching ca. 2% of the total heat soluble protein. We also recovered CC activity from seeds and found that the CC fraction efficiently inhibited both papain and cathepsin H, whereas the corresponding fraction from non-transformed rice seeds showed much lower or undetectable inhibitory activities against these cysteine proteinases. Furthermore, CC prepared from transgenic rice plants showed potent inhibitory activity against proteinases that occur in the gut of the insect pest, Sitophilus zeamais.
The type, incidence, and severity of malabsorption in patients with pancreatic cancer were investigated. The following absorption tests were performed; pancreatic function diagnostant (PFD) test, measurement of serum carotene levels, and 5 g D-xylose absorption test. Rates of abnormality in the tests were 75.7% of 37, 54.2% of 48, and 54% of 50 patients with pancreatic cancer, respectively. In particular, a marked decrease of values in the xylose absorption test was characteristic and more often recognized in patients with carcinoma of the pancreas with occlusion of the superior mesenteric vein. The presence of malabsorption (disturbed transport through the portal vein), in addition to maldigestion of nutrients, is suggested to induce severe malnutrition in patients with pancreatic cancer.
cis-Diamminedichloroplatinum(II) (cisplatin) was intraperitoneally injected into mice bearing SCC VII or EMT6/KU tumors after ten administrations of 5-bromo-2'-deoxyuridine (BrdU) to label all the proliferating tumor cells. The tumors were excised 1 h after the cisplatin injection, minced, and trypsinized. The tumor cell suspensions were then incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus frequency was determined, using immunofluorescence staining for BrdU. Cells that were not labeled with BrdU were regarded as quiescent. The micronucleus frequency in the total number of tumor cells was determined in tumors that had not been pretreated with BrdU. To modify the sensitivity to cisplatin, nicotinamide was intraperitoneally injected before the administration of cisplatin or mice were placed in a circulating carbogen (95% O2, 5% CO2) chamber for 30 min after cisplatin administration. In both tumor systems, the micronucleus frequency in quiescent cells was lower than that in the total cells. Nicotinamide pretreatment increased the micronucleus frequency in total and in quiescent cells in both tumor systems, and to a higher extent in total cells. The combination of nicotinamide and carbogen increased the micronucleus frequency more markedly than treatment with either nicotinamide or carbogen alone. In total cells of both tumors, the nicotinamide injection increased the uptake of [195mPt]cisplatin. The combined treatment raised the uptake more markedly than did treatment with either agent alone. In total cells of the SCC VII tumor, these increases in micronucleus frequency and the [195mPt]cisplatin uptake following nicotinamide or combined pretreatment were significant. In both tumors, carbogen breathing also elevated the micronucleus frequency to some degree in total and quiescent cells and the [195mPt]cisplatin uptake in total cells. The combined nicotinamide and carbogen treatment was considered to be useful for sensitizing tumor cells to chemotherapy with cisplatin in vivo.
The gastric mucosa has been regarded as an active site of humoral immunity since the discovery of Helicobacter pylori. The present study was conducted to determine the in vivo activity of gastric B cells in 53 gastric cancer patients. B-cell activity was measured by protein-A plaque assay, in which IgA-, IgM-, and IgG-plaque-forming cells (PFC) were counted. The number of PFC was associated with the stage of cancer, but the response of lymphocytes in a non-tumorous area (NML) and tumor-infiltrating lymphocytes (TIL) differed. PFC in both sites were decreased compared to n0 cancer in n1 lymph node metastasis-positive cancer, while only NML showed raised PFC in n2 + (P < 0.05, vs TIL). Cancer cells penetrating the submucosa caused the PFC of TIL (but not of NML) to decrease. Invasion of the intratumor capillary (V) or lymphatic (Ly) vessels also caused PFC to change, showing differences of Ig class; there was a decrease of PFC in V2 (IgG- and IgM-PFC) and in Ly2 (all Ig-PFC). IgA-PFC in Ly1 differed in TIL (decrease of PFC) and NML (increase). PFC also differed in TIL and NML in cancer cells, as follows: TIL < NML in tubular and poorly differentiated adenocarcinoma and TIL > NML in papillary and signet ring cell adenocarcinoma. Changes in lymph node (LNL) and blood lymphocytes were similar to those in gastric PFC whose IgA value was 10 times as much as that of LNL. The 5-year survival rate was significantly better in patients with lower rather than higher PFC such as 89% vs 68%. Gastric B cells thus appear to be active and to reflect gastric mucosal immunity.
Severe combined immune deficiency (scid) mice are assumed to have two types of abnormalities: one is high radiosensitivity and the other is abnormal recombination in immunoglobulin and T-cell receptor genes. The human chromosome 8 q1.1 region has an ability to complement the scid aberrations. Moreover, the localization of the subunit DNA-dependent protein kinase [DNA-PKcs] participating in DNA double-strand break repair in the same locus was clarified. In scid mouse cells, the number of DNA-PKcs products and extent of DNA-PK activity remarkably decrease. These observations gave rise to the assumption that DNA-PKcs is the scid factor itself. In order to determine whether the DNA-PKcs gene is the scid gene, we isolated the mouse DNA-PKcs gene and investigated its chromosomal locus by fluorescence in situ hybridization (FISH). Consequently, it became clear that the mouse DNA-PKcs gene existed in the centromeric region of mouse chromosome 16, determined by cross-genetic study, as a scid locus. This finding strongly suggests that mouse DNA-PKcs is the scid gene.
The human Chromosome (Chr) 21q22.1 region contains several genes for cytokines and neurotransmitters and the gene for superoxide dismutase (mutant forms of which can cause familial amyotrophic lateral sclerosis). A region of approximately 5.8 Mb encompassing D21S82 and the glycinamide ribonucleotide transformylase (GART) loci was covered by overlapping YAC clones, which were contiguously ordered by clone walking with sequence-tagged site (STSs). A total of 76 markers, including 29 YAC end-specific STSs, were unambiguously ordered in this 5.8-Mb region, and the average interval between markers was 76 kb. Restriction maps of the YAC clones with rare-cutting enzymes were simultaneously prepared, and the restriction sites were aligned to obtain a consensus restriction map of the proximal region of the 21q22.1 band. The restriction map made from 44 overlapping YACs contains 54 physically assigned STSs. By integrating the consensus map of the adjacent 1.8-Mb region, we obtained a fine physical map spanning 6.5 Mb of human Chr 21q22.1. This map contains 24 precisely positioned end-specific STSs and 12 NotI-linking markers. More than 39 potential CpG islands were identified in this region and were found to be unevenly distributed. This physical map and the YACs should be useful as a reference map and as a resource for further structural analysis of the Giemsa-negative band (R-band) of Chr 21q22.1.
A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given orally to 14 patients. The daily dose ranged from 0.5 to 2.0 g and the total dose given ranged from 0.8 to 28 g/m2. Possible toxicities observed were vomiting in two patients, muscle cramping in one and multiple joint pain in one. All these complications were mild and transient and no other toxicity was observed. The peak serum concentration of KU-2285 was 25-30 micrograms/ml at the dose of 1 g/m2. The cumulative toxicity of KU-2285 appears to be relatively low and further clinical trials seem to be warranted.
Ten patients aged 3 to 13 years (mean, 9 years and 7 months) underwent forearm lengthening by callotasis. The indications for lengthening were shortening and/or deformity of the forearm due to exostosis of the distal ulna in five cases, enchondroma of the distal ulna in one, growth disturbance after fracture of the distal radius in one, radial club hand in one, congenital amputation of the forearm in one and congenital dislocation of the radial head in one. Four had lengthening of the ulna, one of the radius and five of both the radius and the ulna. The average lengthening achieved was 30 mm. Complications encountered were pin track discharge in three cases, callus fracture in five, delayed consolidation of the callus in one and no callus formation in one. Review after 1 to 7 years follow-up (with a mean of 4 years and 9 months) showed satisfactory improvement in appearance and function especially in patients who had tumorous conditions or traumatic epiphyseal arrest.
The anti-carcinogenic effect of TAP-144-SR biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent LHRH agonist, TAP-144 (D-Leu6-(des-Gly10-NH2)-LHRH ethylamide, leuprolide acetate) was investigated in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumours. At 50 days of age, all rats were given 20 mg doses of DMBA by gastric intubation. Rats on the Initiation Group were given a single s.c. injection of TAP-144-SR (3 mg/kg) 1 week before DMBA treatment, and rats in the Promotion Group were given repeated s.c. injections every fourth week from 1 week after DMBA treatment until the end of the experiment. In the Initiation Group, tumour incidence and multiplicity were reduced to 20.8% and 15.0% of the Control Group values, respectively. In the Promotion Group, tumour incidence and multiplicity were also reduced to 17.7% and 7.9%, respectively. It was suggested that TAP-144-SR may be a potential candidate as an agent for hormonal chemoprevention in breast cancer.