Acceleration of actin polymerization by actin-coated latex particles.
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Biomedical subjects
Publications and source records attributed to T Yamane.
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The structure of Bowman-Birk type protease inhibitor (A-II from peanut) is described at 3.3 A resolution. The molecules form a tetramer with 222 local symmetry in our crystals. Each monomer has an elongated shape with approximate dimensions of 45 X 15 X 15 A and consists of two distinct domains. The three-dimensional structures of the two domains are similar and are related by the intramolecular approximate twofold rotation axis. The two independent protease binding sites protrude from the molecular body on opposite sides. A scheme for the molecular evolution of the double-headed Bowman-Birk type protease inhibitors is proposed, based on the three-dimensional structure.
We tested the combination of mitoxantrone, etoposide, cisplatin, and prednisolone as salvage treatment for patients with advanced aggressive non-Hodgkin's lymphoma. Among 18 evaluable patients, four complete and seven partial responses were observed, for an overall response rate of 61%. The median duration of response was 36 weeks (range, 11-58). The median survival time from the beginning of the regimen was 52 weeks for responders and 24 weeks for nonresponders. Myelosuppression was the major dose-limiting toxic effect; however, it was generally well-tolerated. These results indicate that the combination regimen can play a role in the treatment of relapsed or resistant non-Hodgkin's lymphoma.
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Twenty-two patients with non-Hodgkin's lymphoma were treated with a four-drug combination of mitoxantrone, etoposide, cisplatin and prednisolone (MEPP) after their disease had failed to respond to, or had relapsed after, induction chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone with/without bleomycin (CHOP/CHOP-bleo). Of 18 evaluable patients, four (22%) achieved complete remission and six (33%) responded partially. The median duration of response was 29 weeks (range, 9 to 54 weeks). The median survival time was 45 weeks for responders and 22 weeks for non-responders. Gastrointestinal toxicity was common, but well tolerated. Myelosuppression was the major dose-limiting toxicity: 11 patients (61%) experienced a febrile episode during periods of neutropenia and two patients, both of whom had massive bone marrow involvement of the disease, succumbed to infection. Despite the moderate to severe myelotoxicity, these results provide evidence that MEPP is an effective regimen for non-Hodgkin's lymphoma resistant to CHOP or CHOP-bleo.
Proliferation and death of androgen- and estrogen-responsive cells in seminal vesicles were compared between neonatally and adult (on Day 60 after birth) castrated mice. Daily injections of either testosterone propionate (TP) or estradiol-17 beta (E2) were started on Day 90 after birth; the incorporation of 5-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) into the whole seminal vesicles was used as an index for proliferation. Although the peak of [125I]IdUrd uptake was observed 3 days after starting TP injections in both neonatally and adult castrated mice, the peak was lower and the period of proliferation was much longer in the former than in the latter. When TP injections were stopped, the fraction of surviving cells that synthesized DNA on Day 3 of TP injections was much larger in neonatally than adult castrated mice. The difference was attributed to the presence of TP-induced proliferation of fibromuscular cells in the neonatally castrated mice but not in the adult castrated mice; only the fibromuscular cells but not epithelial cells survived after stopping TP injections. Although injections of E2 increased the proliferation of epithelial cells but did not the weight of seminal vesicles in adult castrated mice, the same procedure increased the proliferation of both epithelial and fibromuscular cells and the weight in neonatally castrated mice. The E2-induced fibromuscular cells seemed to survive in the presence or absence of E2. The present results seem to indicate that androgen- and estrogen-induced proliferation of fibromuscular cells is irreversible in seminal vesicles of neonatally castrated mice and that the depletion of androgen in the seminal vesicle during neonatal and prepubertal periods is at least in part compensated by the administration of androgen, even after 90 days of age.
The purpose of this study is to examine effects of methylnitrosourea (MNU) on electron microscopic visualization of acridine orange (AO) binding to DNA in mouse lymphoma L-1210 cells and to demonstrate alteration of the euchromatin/heterochromatin ratio by morphometry. [3H] uridine uptake into RNA molecule is inhibited and percentage of AO positive cells is decreased to approximately 20% of that of the untreated control cells by treatment of the lymphoma cells with MNU. When the MNU-treated cells are cultured in the presence of 3-amino-benzamide, a specific inhibitor of poly(ADP-ribose) synthetase, the depression in RNA synthesis is prevented, and percentage of AO positive cells as well as numbers of AO chromatin interaction products per single cell nucleus are also completely recovered as compared to those in the untreated cells. In the MNU-treated cells the decreased number of AO positive cells coincides with a reduced [3H] uridine uptake as well as with a lowered euchromatin/heterochromatin ratio. The results suggest that visualization of AO chromatin interaction products in the proliferating cells is related not only to RNA synthesis in the cells, but also to the euchromatin/heterochromatin ratio.
Crystallization and preliminary crystallographic study of Bowman-Birk type protease inhibitors, A-I, A-II, and B-III from peanut seeds (Arachis hypogaea), and of the A-II + trypsin complex were carried out. A-II, with 70 amino acid residues, crystallizes in a trigonal system, P3(1)21 (or P3(2)21), a = 71.8, c = 65.9 A, Z = 12 or 18. The A-I crystal is isomorphous with that of A-II, indicating that the N-terminal residues are in a disordered state in both crystals. The B-III crystal is monoclinic, C2, a = 119.6, b = 69.6, c = 94.2 A, beta = 115.1 degrees, Z is about 40. The A-II + trypsin complex crystallizes in an orthorhombic system, P2(1)2(1)2(1), a = 55.5, b = 56.0, c = 182.1 A, Z = 4.
The crystal structure of the complex formed by bovine trypsin and Bowman-Birk type protease inhibitor AB-I extracted from azuki beans (Vigna angularis) 'Takara' has been analyzed. The structure was solved by the application of the phase combination of single isomorphous phases and trypsin model phases, followed by phase improvement using the iterative Fourier technique. From the resulting electron density map, a three-dimensional atomic model of the trypsin binding domain of AB-I has been built. The peptide chain at the trypsin reactive site turns back sharply at Pro29 and forms a 9-residue ring (Cys24-Cys32). The 'front side' of this ring, consisting of the reactive site (Cys24-Met28), interacts with trypsin in a similar manner to other families of inhibitors and forms a stable complex, which seems to be maintained by the interactions with the 'back side' of this ring (Pro29-Cys34). The similar spatial arrangements of the 'back side' of this inhibitor and the 'secondary contact region' of the other inhibitors with respect to the reactive site suggest an important common role of these regions in exhibiting inhibitory activity.
The purpose of this study was to examine the effects of actinomycin D on localization of acridine orange (AO) binding to DNA in rat astrocytoma C6 cells and to discuss briefly the significance of AO chromatin interaction products. Actinomycin D markedly inhibited 3H-uridine incorporation into RNA and the percentage of AO positive cells was reduced to approximately 40% of that of the untreated control cells, whereas no distinct decrease of 3H-thymidine incorporation was induced by actinomycin D. Electron microscopic radioautography combined with the AO ultracytochemistry revealed that silver grains indicating binding of 3H-actinomycin D are located mostly over the euchromatin portion near the segregated nucleolus and heterochromatin and that no or only a few AO chromatin complex was found in nuclei labeled heavily with 3H-actinomycin D. These results of the present study together with the results of the previous studies seem to indicate that AO might selectively bind to active or derepressed DNA template sites for DNA dependent RNA polymerase in the euchromatin portion of the cell nucleus.
An autopsy case of clostridial gas gangrene occurring in a 54-year-old man with colon adenocarcinoma, liver cirrhosis, and diabetes mellitus is reported. The patient died 4 days after the onset of symptoms with episodes of vomiting and abdominal pain. Gangrene of both hips and perineum, hemolysis, renal failure, and disseminated intravascular coagulation were the dominant clinical features. Clostridium septicum was isolated from the subcutaneous tissue fluid. Adenocarcinoma of the ascending colon with ulceration found at autopsy was supposed to be an entry of the organism. Histologically, lesions of subcutaneous tissue and muscles were characterized by the absence of inflammatory infiltrates in spite of extensive necrosis. A summary of 35 cases of gas gangrene hospitalized to the Osaka University Hospital for the past 16 years indicates that clostridial gas gangrene patients with underlying diseases such as malignant neoplasm, diabetes, liver cirrhosis or immunodeficiency have a relatively poor prognosis.
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In order to clarify the influence of hyperthermia on the uptake of anticancer drugs into cancer cells, ddy mice and 3H-labelled 5-fluorouracil (3H-5-FU) were used. The Ehrlich ascites cells (E-cells) in addition to 3H-5-FU were heated in vitro at different temperatures and the uptake of the 5-FU into E-cells were observed with the passage of time, while 3H-5-FU was given to an E-cell "planted mice, to which local and total-body hyperthermias were performed at different temperatures for the uptake of the 5-FU into the Ehrlich solid tumors to be measured at intervals. The uptakes of 5-FU into E-cells and the Ehrlich solid tumors was observed by 3H-5-FU uptake and autoradiography respectively. The results are summarized as follows: 1) There was a significant sthenia of the 5-FU uptake into E-cell, as it was heated in vitro at 43 degrees C for 30 minutes and 60 minutes. This result was confirmed by autoradiograph. The sthenia was only found in E-cells remarkably, and not in normal cells. 2) In a tumor bearing mouse, there was a significant sthenia of the 5-FU uptake into the Ehrlich solid tumors as it was heated at local hyperthermia (42 degrees C) and total-body hyperthermia (42 degrees C) for 30 minutes and 60 minutes. The result was confirmed by autoradiograph. The sthenia was only found in the Ehrlich solid tumors remarkably, and not in normal tissues. This results show an antiplastic increment by hyperthermochemotherapy that anticancer drugs can be included into the cancer cells and the Ehrlich solid tumors more easily by heating.
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