Electronic structure of super-honeycomb systems: A peculiar realization of semimetal/semiconductor classes and ferromagnetism.
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Journal Article↗
Biomedical subjects
N Shima
Publications and source records attributed to N Shima.
Chemotherapeutic effects of intra-arterial administration of ACNU in primary intracerebral non-Hodgkin's lymphoma.
The authors report five patients with primary intracerebral non-Hodgkin's lymphoma who were treated with several cycles of intra-arterial injection of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) at doses of 80 to 100 mg/m2/injection at several monthly intervals. There was no simultaneous use of steroids, and no patients had concomitant immunosuppression; no patient was human immunodeficiency virus positive. This therapy was initially used in four patients with advanced recurrent lymphoma. These patients experienced tumor progression despite our institutional standard therapy comprising cranial irradiation followed by repeated courses of systemic multi-agent chemotherapy (cyclophosphamide, vincristine, adriamycin, and prednisolone) more than 3 months previously. Based upon brain computed tomography scans and clinical neurologic examinations, three of the four cases showed partial responses ranging from 10 to 12 months in duration, whereas the other patient remained stable without worsening for 8 months. A fifth case was particularly noteworthy; this patient had no prior therapy and intra-arterial chemotherapy alone induced an 18-month, disease-free remission. No significant therapy-related complications nor neurotoxicity were seen. These results suggest that intra-arterial administration of ACNU may be a potential candidate for intracerebral lymphoma therapy.
Adult↗
Tumor cytotoxic activity of HGF-SF.
IMR-90 human embryonic lung fibroblasts secrete a tumor cytotoxic factor. This factor, termed F-TCF, is moderately cytotoxic in human tumor cell lines (KB, MCF-7, BG-1) and is very cytotoxic in mouse tumor cell lines (Sarcoma 180, Meth A sarcoma, P388). The cytotoxicity depends on the initial target cell number and is due to cytostasis rather than cytolysis. F-TCF was purified from conditioned medium by a combination of UF-concentration, CM sephadex C-50, Con A sepharose, Mono S cation-exchange and heparin sepharose chromatography and exhibited a molecular mass (M(r)) of 76 to 80 kD on SDS-PAGE under non-reducing conditions. F-TCF is a heterodimer composed of a large alpha-subunit with M(r) 52 to 56 kD and a small beta-subunit with M(r) 30 to 34 kD. F-TCF is a heparin-binding, heat-labile, basic glycoprotein (pI 7.4-8.6). Its activity is stable over the pH range of 6.0 to 9.0, but is completely lost after reduction with 2-mercaptoethanol. Protein sequencing indicates that the alpha-subunit is blocked at the aminoterminus. The primary amino acid sequences deduced from hepatocyte growth factor (HGF) cDNAs cloned from human placenta and liver cDNA libraries indicate that F-TCF is identical to the placenta type HGF in the aminoterminal sequence of the beta-subunit, but differs at two sites from the liver type HGF. Two forms of F-TCF cDNA were found in an IMR-90 human fibroblast cDNA library. One form was identical to placenta type HGF cDNA and the other was a variant with a 15 base pair deletion in the coding region. In addition, mRNA corresponding to the deleted form of cDNA was present in total RNA prepared from IMR-90 cells. F-TCF was thus identified as placenta type HGFs including a variant. The deleted form of recombinant HGF (rHGF) expressed in CHO cells had slightly lower heparin-binding affinity than did the intact form. Both rHGFs had almost the same dose-response curves for cytotoxicity in Sarcoma 180 or Meth A sarcoma cells. Moreover, rHGF (the deleted form) was cytotoxic in hepatocellular carcinoma cells (HepG2, Hep3B, H35). Dose-response curves for the stimulation of DNA synthesis in rat hepatocytes by HGFs were very similar up to about 12.5 ng/ml, but differed significantly at higher concentrations. The deleted form gave maximal activity in a dose range of 12.5 to 100 ng/ml and had about 1.4- to 1.9-fold higher specific activity in that range than the intact form did.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
[Structure and biological property of fibroblast-derived tumor cytotoxic factor (F-TCF)].
Fibroblast-derived tumor cytotoxic factor (F-TCF), isolated from human embryonic lung fibroblasts, is cytotoxic against various human and mouse tumor cells. Physicochemical and biological properties indicate that F-TCF is closely similar to hepatocyte growth factors (HGFs), cDNAs of which are isolated from human liver and placenta. Isolation and expression of F-TCF cDNA revealed that F-TCF was identical to the placenta type HGFs, including a variant with a deletion of 15 base pairs in the coding region. The deleted form of recombinant HGF (rHGF) had slightly lower heparin binding affinity than the intact form. Specific activities of rHGFs were almost the same in tumor cytotoxic activity, but different in hepatocyte growth stimulating activity. These results indicate that deletion of five amino acids results in conformational change which alter biological activity.
Amino Acid Sequence↗
Tumor cytotoxic factor/hepatocyte growth factor from human fibroblasts: cloning of its cDNA, purification and characterization of recombinant protein.
Two different forms of cDNA for F-TCF were isolated from cDNA library prepared with mRNA from human embryonic lung fibroblast, IMR-90 cells. One of them was completely identical to the cDNA for placenta type hepatocyte growth factor (HGF) and the other one was a variant cDNA for the HGF with a deletion of 15 base pairs in the coding region. The cDNAs were expressed in CHO cells and recombinant proteins were purified and characterized. The deleted form of recombinant F-TCF (rF-TCF) was slightly lower in heparin affinity than the intact form. Both rF-TCFs showed almost same dose-response curves for cytotoxicity on Sarcoma 180 or Meth A sarcoma cells. Dose-response curves for the stimulation of DNA synthesis in rat hepatocytes were also almost same before reaching maximal activity at 12.5 ng/ml but significantly different at higher concentrations. The deleted form of rF-TCF maintained maximal activity in the dose range of 12.5 to 100 ng/ml, although the intact form decreased the activity dose-dependently at more than 25 ng/ml. This suggests that the deletion of five amino acids results in a conformational change which alters heparin binding and hepatocyte growth stimulating activities.
Amino Acid Sequence↗
Hepatocyte growth factor modulates migration and proliferation of human microvascular endothelial cells in culture.
Epidermal growth factor (EGF) induces tubular formation of cultured human omental microvascular endothelial (HOME) cells and EGF also stimulates cell migration as well as expression of tissue type plasminogen activator (t-PA). Here we studied the effects of hepatocyte growth factor (HGF) on cell proliferation, cell migration and expression of t-PA and other related genes. Migration of confluent HOME cells into the denuded space was stimulated by HGF after being wounded with razor blade, but at a reduced rate in comparison with EGF. HOME cells could be proliferated in response to exogenous 100 ng/ml of HGF at rates comparable to that of 20 ng/ml EGF. The chemotactic activity of HOME cells was significantly stimulated by HGF in a dose-dependent manner when assayed by Boyden chamber. HGF did not efficiently enhance expression of both the t-PA gene and a tissue inhibitor of metalloproteinase gene whereas it stimulated expression of plasminogen activator inhibitor-1. Our present study provides a new evidence that some of the biological effects of HGF on HOME cells in culture are similar to those of EGF.
Bilirubin↗
Electronic structure of DNA by DV-X alpha cluster calculations. I. d(GG).d(CC), d(CG)2, d(GC)2 A and B conformations.
The electronic structure of d(GG).d(CC), d(CG)2, d(GC)2 which are stacked base pairs in the DNA double helix, are elucidated for both A and B conformations in detail by DV-X alpha cluster calculations. These three DNA double helix fragments are constructed from the same bases, G and C, but the electronic structure of the fragments for A and B conformations differs from each other characteristically. In particular, the electronic states of the O2 and O3 in phosphates differ drastically from each other, and might play a crucial role as recognition sites in various reaction processes concerning DNA. These differences are caused by the delicate differences in the admixture of the orbital components and the intra- and inter-bases interactions. Contour maps of the wavefunction of the HOMO and LUMO are compared among the stacking isomers.
Animals↗
ELISA for F-TCF (human hepatocyte growth factor/hHGF)/fibroblast-derived tumor cytotoxic factor antigen employing monoclonal antibodies and its application to patients with liver diseases.
For determination of fibroblast-derived tumor cytotoxic factor, F-TCF (human hepatocyte growth factor/hHGF), sensitive two-step sandwich enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibodies was developed. Microplates were coated with monoclonal antibody (P1C8) and bound F-TCF was quantitated with the second monoclonal antibody (P2D6) linked to peroxidase. The standard curve for F-TCF was found to be linear in the range of 0.16 to 10 ng of F-TCF per ml. The assay was specific for F-TCF but not for plasminogen. The assay can be used for determination of F-TCF antigen in both human plasma and serum. The variation of absorbance was little in duplicate samples. Recoveries of exogenous F-TCF added to serum or plasma samples showed theoretical values. F-TCF antigen levels in 21 healthy volunteers was found to be 0.56 +/- 0.43 ng/ml. In contrast, mean F-TCF levels in patients with liver diseases were all higher than those of healthy subjects. This ELISA system has the advantage of using a sensitive and reproducible set of monoclonal antibodies, and is a useful method for monitoring F-TCF levels in patients with liver diseases.
Animals↗
A radiotherapeutic experience for localized extranodal non-Hodgkin's lymphoma: prognostic factors and re-evaluation of treatment modality.
Between 1966 and 1988, 149 patients were treated with radiotherapy for localized extranodal lymphoma. The average total dose given was 39.8 Gy for low grade disease and 48.7 Gy for all other disease. Of the 149 patients, 60 also received adjuvant chemotherapy. Twenty-four had low grade lymphoma, 109 had intermediate grade disease, and 16 had high grade disease, histologically. The distribution of histological grade and T/B phenotype varied with the primary site. Low grade lymphomas were found mainly in the orbit, and T-cell lymphomas were found in the nasal cavity and nasopharynx. The 5-year survival rates according to tumor location were 89% for oral cavity, 86% for paranasal sinus, 83% for thyroid, 69% for orbit, 47% for Waldeyer's ring (WAR), 44% for testis, 23% for CNS, 21% for nasal cavity and 60% for other sites. Histological grade and T/B phenotype both had prognostic importance. Combined chemotherapy significantly improved the survival rate only for disease with intermediate or high grade histology. Other prognostic factors according to the primary site were the bulk of lymph node for WAR disease, the radiation dose for CNS disease, bone erosion for orbital disease, stridor for disease of the thyroid, and the tumor stage for disease of both the testis and the thyroid.
Adolescent↗
A fibroblast-derived tumor cytotoxic factor/F-TCF (hepatocyte growth factor/HGF) has multiple functions in vitro.
We previously demonstrated that a tumor cytotoxic factor(F-TCF) purified from the culture broth of human embryonic lung diploid fibroblast, IMR-90 cells was one of the human hepatocyte growth factors (hHGFs). In the present report, we demonstrate its biological functions. F-TCF showed moderate cytotoxicity on human tumor cell lines KB, BG-1, MCF-7 and Hs913 T, and strong cytotoxicity on mouse tumor cell lines Sarcoma 180, Meth A sarcoma and P388. On the contrary, F-TCF was a potent mitogen not only for adult rat hepatocytes, but also for human endothelial cells, HUVEC and human melanocytes. Moreover, F-TCF induced the differentiation of premyelocyte leukemia, HL-60 cells into morphologically granulocyte-like cells. These biological functions suggest that F-TCF is an effector molecule responsible for inflammation and repair in injured tissues including tumor and liver.
Animals↗
Role of Ca2+ in t-PA production by human embryonic lung diploid fibroblast, IMR-90 cells, stimulated by proteose peptone.
Proteose peptone (p.peptone) remarkably induced tissue plasminogen activator (t-PA) activity in the conditioned medium of confluently cultured human embryonic lung diploid fibroblast, IMR-90 cells, in a dose-dependent manner. t-PA activity correlated well with the amount of t-PA antigen found in the conditioned medium of IMR-90 cells stimulated by p.peptone. t-PA production by IMR-90 cells stimulated by p.peptone was dependent on extracellular Ca2+ concentration and maximum t-PA production required approximately 3.6 mM extracellular Ca2+. Conversely, elimination of Ca2+ from the culture medium by EGTA, Ca2+ chelate agent, strongly inhibited t-PA production induced by p.peptone. t-PA production induced by p.peptone was inhibited in a dose-dependent manner by Verapamil, which inhibits Ca2+ uptake through the slow channels and also by W-7, an inhibitor of calmodulin. These results suggested that influx of extracellular Ca2+ into IMR-90 cells was caused by p.peptone and induced t-PA production by the cells.
Binding, Competitive↗
Extranodal non-Hodgkin's lymphoma of the head and neck. A clinicopathologic study in the Kyoto-Nara area of Japan.
The clinicopathologic features of 114 Japanese patients with extranodal non-Hodgkin's lymphoma of the head and neck region were analyzed. The median age was 60.5 years and the male:female ratio was 1.5:1. The most common site of involvement was Waldeyer's ring, followed by the oral cavity, thyroid gland, paranasal sinuses, nasal cavity, and larynx. Seventy-five percent of the patients were in Stage I or Stage II at admission. Histologically, diffuse lymphoma accounted for 94% and follicular lymphoma for 6% of cases. The histologic grade according to the Working Formulation System of the National Cancer Institute was low in 11%, intermediate in 75%, and high in 14% of cases. Immunohistochemical study showed that the majority of the cases were of B-cell type and only 13 cases (11%) were of the T-cell type. Peripheral T-cell lymphomas (eight cases) mainly occurred in the nasopharynx and nasal cavity, whereas four of five thymic T-cell lymphomas were found in the palatine tonsil. The over-all 5-year survival rate was 54%, and the factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage, and the site of initial presentation. Five-year survival with nasal cavity and Waldeyer's ring lymphoma was 24% and 46%, respectively. The poor prognosis of lymphomas at these sites might result from the predominance of T-cell lymphoma, the paucity of low grade lymphoma, and the relatively high incidence of cases that were in an advanced stage at presentation. In Stage II, patients treated with combined therapy tended to have a better 5-year survival rate than those treated with radiotherapy alone.
Adolescent↗
Identity of a tumor cytotoxic factor from human fibroblasts and hepatocyte growth factor.
Human embryonic lung diploid fibroblast, IMR-90 cells secreted a tumor cytotoxic factor. The fibroblast-derived tumor cytotoxic factor (F-TCF) has a cytotoxic activity to Sarcoma 180 and a cytostatic and degenerative activities to KB cells. F-TCF has been purified about 540,000-fold with 23.3% recovery from 75 liters of the conditioned medium containing 5% newborn calf serum. The purified F-TCF is a basic glycoprotein with isoelectric point values of 7.4 to 8.6. It was stable in the pH range from 6.0 to 9.0 and was stable at the heating temperature of 60 degrees C for 10 min, but completely inactivated by reducing it with 2-mercaptoethanol. F-TCF has molecular weight of 76 to 80 kD on SDS-PAGE under non-reducing conditions and is a heterodimer consisting of a large alpha subunit with 52 to 56 kD and a small beta subunit with 30 to 34 kD. F-TCF was identified as one of human hepatocyte growth factors by the physicochemical properties including N terminal and a few internal amino acid sequences. We have confirmed that F-TCF has an ability to dramatically stimulate DNA synthesis in adult rat hepatocytes in the low dose range of 1 to 10 ng/ml.
Amino Acid Sequence↗
Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy.
Thirty patients with histologically proven primary intracranial non-Hodgkin's lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation-chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30-40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.
Adolescent↗
Malignant lymphoma of the central nervous system in Japan: histologic and immunohistologic studies.
Ninety-seven Japanese patients with so-called primary non-Hodgkin's lymphoma of the central nervous system (CNS-NHL), unrelated to the acquired immunodeficiency syndrome (AIDS) or organ transplantation, were reviewed. The patients' ages ranged from 1 to 87 years (median: 58 years) with a male to female ratio of 1.77:1. The most frequent past histories were acute appendicitis (appendectomy), head injury, uveitis or iritis, and gastritis or gastric ulcer. These patients presented with symptoms suggesting an expanding intracranial lesion with no signs of extracranial lymphomatous disease. Combined computed tomographic scans, angiography, and findings at surgery or autopsy showed that the cerebrum was the commonest site of involvement, 87% of all cases, with the frontal to temporal region being the most commonly involved. Histologically, the diffuse large-cell type was most frequent and 26% of lymphomas were of high-grade malignancy as defined by the Working Formulation. The reported frequency of high-grade CNS-NHLs in AIDS patients in the United States is much higher (over 60%). Immunohistochemistry on paraffin-embedded sections revealed a B-cell nature of the present series of tumors. In 16% of the cases, large numbers of small lymphoid cells with a positive reaction predominantly for anti-T lymphocyte antibodies surrounded the tumors or aggregated around the capillaries. The tumors which were infiltrated by small lymphoid cells showed more favorable prognosis than those which were not, suggesting a host reaction to tumor growth in these patients.
Acquired Immunodeficiency Syndrome↗
Intracerebral malignant lymphoma with fluctuating regression and spatial evolution.
Seven patients with histologically proven primary intracerebral malignant lymphoma, characterized by a fluctuating nature with both transient regression and spatial evolution of the tumors without contiguity to the initial lesion, are presented. Although the overall outcome was unfavorable, two cases had a long-term survival of 3 years or more and one of them showed a good quality of life. Correlation among characteristic clinical presentations, computed tomography scans, and prognostic factors after management with surgery, radiation, and chemotherapy, including steroids, is discussed.
Aged↗
[Investigation of 121 cases of spinal anesthesia with plain 0.5% bupivacaine].
Bupivacaine has been used for spinal anesthesia since 1982 in our department. We performed a retrograde investigation of 121 cases who had lower limb surgery and anesthetized with plain 0.5% bupivacaine solution during the year of 1987. Doses of bupivacaine, maximum spread of analgesia and spinal tap level were analyzed. We chose the bupivacaine doses from 2.5 ml to 4.0 ml depending on the condition of the patient and the specificity of the surgery. The patients were divided into 3 groups by the dose of bupivacaine: i.e. 3.0, 3.5, 4.0 ml of plain 0.5% bupivacaine. Seventy percent of all patients had a spinal tap on L3/4 interspace. The average upper level of analgesia was T7 in each group and no patient had analgesia above T2 level. There was no correlation between the site of injection and volume of local anesthetics. However patient's physical status and surgical procedure are more important to obtain the good analgesic level. There was no significant respiratory depression nor hypotension during and after the surgery. It is concluded that 3-4 ml of 0.5% bupivacaine provided satisfactory spinal anesthesia for the lower limb surgery.
Anesthesia, Spinal↗
Electronic states of Si(100) reconstructed surfaces.
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Journal Article↗