Thirty-six patients who were admitted for surgical resection of leiomyosarcomas of the gastrointestinal tract to the Department of Surgery II, Kanazawa University Hospital, Kanazawa, Japan and its affiliates are included in the study. Follow-up data on survival is available for 32 patients. The clinico-pharmacologic variables, such as tumor site, tumor size, cellularity, mitotic index, and DNA ploidy pattern were analyzed and the results proved to correlate with the prognosis. Thirteen (41%) of the patients presented with distant metastases and/or recurrences, with hematogenous metastasis being the predominant type of recurrence. Local recurrences and/or distant metastases were significantly correlated with survival (p less than 0.001), as was tumor site (p less than 0.03), tumor size (p less than 0.04), surgical treatment (p = 0.05), and DNA ploidy pattern (p = 0.06). Neither the mitotic index nor the cellularity proved to be significantly correlated with survival. Furthermore, some of the patients with local recurrences or distant metastases survived long after resection of recurrent tumors. In view of the results, aggressive surgical resection may be an efficient treatment of recurrences.

Adult↗

PubMedDate not supplied

Simultaneous exposure to interleukin-18 and interleukin-10 in vitro synergistically augments murine spleen natural killer cell activity.

Interleukin-18 (IL-18) enhances interferon gamma (IFNgamma) production and natural killer (NK) cell activity, and elicits protective antitumor effects in vivo. IL-18 and IL-12 synergistically augment IFNgamma production reportedly because IL-12 enhances IL-18 receptor (IL-18R) expression. We now show that IL-18 also synergizes with IL-10 to augment murine splenic NK activity against Yac-1 cells in a standard 4-h chromium-release assay, but IFNgamma production is only slightly enhanced. This pattern of NK activity was also observed with severe combined immunodeficient (SCID) mouse spleen cells indicating that the cytokines were not acting on T or B cells. The cytokines had no priming activity on the spleen cells and, when cells were left unstimulated for 24 h in culture, little NK activity was induced when IL-18 was added for the next 24 h. The reverse transcriptase/polymerase chain reaction revealed that IL-18 receptor (IL-18R) mRNA was expressed early during in vitro spleen cell culture but none was expressed after culture for 24 h regardless of the stimulus. Binding of 125I-labeled IL-18 revealed that exposure to IL-10 only slightly increased IL-18R expression. Expression of perforin mRNA was constitutive and was unaffected by the cytokines; however, Fas ligand (FasL) mRNA expression was strong in cultures with IL-18 alone or combined with IL-10. When Fas-expressing cells and their parental cells were used as targets, weak Fas-mediated cytolytic activity was observed after exposure to IL-18, and this was further enhanced by combination with IL-10. Finally, the augmentation of NK activity was abrogated by the inhibitor concanamycin A, indicating that the enhanced NK activity is perforin-dependent.

Animals↗

PubMedDate not supplied

Immunologically defined component of the circumferential ring around the cuticular plate in mammalian hair cells.

A monoclonal antibody (CAR) was raised by in vitro immunisation to a component of the circumferential actin ring that is associated with the apical junctions encircling the cuticular plates of mammalian hair cells. On western blots it bound a protein band at about 42 kD, equivalent to the normal location of actin, but it did not label the paracrystalline bundle of actin filaments in the stereocilia, the complex actin filament gel that forms the cuticular plate or the filamentous actin in the cell cortex. When applied to whole mounts of the auditory sensory epithelium in the guinea pig it provided a clear, unambiguous map of the distribution of inner and outer hair cells. In this respect, it can provide an accurate guide to patterns of hair cell differentiation and repair. CAR cross-reacted with the membrane-associated cytoskeleton in selected cells from a wide range of other tissues.

Actins↗

PubMedDate not supplied

Histogenetic stereological reconstruction of rat basophilic, clear, and oncocytic neoplastic renal cell lesions using carbonic anhydrase type II-PAS double-stained sections.

The histogenesis of 3 types of rat renal cell tumors (basophilic cell, clear cell, and oncocytic) was stereologically analyzed, with particular attention paid to transitions from normal tubules. Early nitrosamine-induced preneoplastic lesions, including dysplastic tubules (altered tubules), epithelial hyperplasias, and small adenomas, were reconstructed using serially sectioned specimens processed for carbonic anhydrase type II (CA) and periodic acid-Schiff (PAS) (CA-PAS) double staining to allow easier distinction of the nephron segments: Proximal tubules had a PAS-positive brush border and were weakly positive for CA in the cytoplasm; distal tubules were PAS negative and weakly positive for CA; collecting ducts were PAS negative and strongly positive for CA. Similarly, cytochrome c oxidase (CytOx) and CytOx-PAS double staining was also applied to confirm the character of oncocytic lesions. All basophilic lesions (7 of 7) showed transition to proximal tubules. Clear cell lesions positive for CA, on the other hand, showed transition to distal tubules in 4 of 9 (44.4%) lesions and to collecting ducts in 4 of 9 (44.4%) lesions, but in only 1 of 9 (11%) to a proximal tubule. All oncocytic lesions (16 of 16), characterized by positivity for both CA and CytOx, showed transition to collecting ducts. The results indicate that the origins of renal cell neoplasia are proximal tubules for the basophilic cell lesions, either proximal or distal tubules for their clear cell counterparts, and collecting ducts for oncocytic lesions.

Adenocarcinoma↗

PubMedDate not supplied

Reaction mechanism of protocatechuate 3,4-dioxygenase.

We have observed that high SOD-like function (decomposition of superoxide anion) was observed for several iron(III) compounds with tripodal ligands and several oxovanadium(IV) compounds, and also that these compounds exhibit high catalytic activity for oxidative cleavage of 3,5-di-tert-butylcatechol in non-donating solvents such as dichloromethane or nitromethane. These are suggesting that the same reaction intermediate exists in reaction mixtures of both the SOD-like and catecholase-like functions of these compounds. Based on these facts, we have proposed a new reaction mechanism for the oxidative cleavage of catechol catalyzed by the native non-heme iron dioxygenases; this includes formation of an iron(III)-peroxide adduct as a reaction intermediate, which exhibits electrophilic nature.

Binding Sites↗

PubMedDate not supplied

Comparison on reactivity of Fe(III) and Al(III) compounds in the presence of hydrogen peroxide: its relevance to possible origin for central nervous system toxicity by aluminum ion.

The iron(III) compounds with several aminocarboxylate chelates containing an aryl or furan substituent exhibit high activity in enhancement of the reactivity of hydrogen peroxide, leading to facile hydroxylation at benzene ring, and to degradation of furan ring, but no such activity was observed for the corresponding Al(III) compounds. These results were interpreted in terms of the molecular orbital consideration, and lack of the activity of the Al(III) complexes was attributed to lack of electrophilic nature of the peroxide adduct due to the absence of a d-orbital; this may explain the fact that there were no tumors in Al-NTA(nitrilotriacetic acid)-treated rats. Based on the facts observed in this study, the decreased function of iron(III) ions for synthesizing neurotransmitters in the brain was assumed to be one of the possible origin for the neurotoxicity by injection of the Al(III) salts in vivo.

Aluminum↗

PubMedDate not supplied

Contribution of a peroxide adduct of copper(II)-peptide complex to modify the secondary structure of albumin.

We have found that copper(II) compounds containing a peptide group in the chelate exhibit high activity for modification or degradation of albumin in the presence of hydrogen peroxide, whereas no activity was detected for the copper(II) compounds without an amide-group. It is suggested that presence of the amide-group in the ligand may play an important role in the formation of a peroxide adduct and in activation of the peroxide ion, leading to cleavage of the peptide bond of a neighboring protein. It is implied that conversion of normal cellular prion protein PrPC into a disease-causing isoform, PrPSc is attributed to the activated peroxide ion coordinated to a copper(II) captured in the NH2-terminal domain of the PrPC.

Carbonic Anhydrases↗

PubMedDate not supplied

Mechanism of double-strand DNA cleavage effected by iron-bleomycin.

We have observed that in the absence of hydrogen peroxide the Fe(III)-bleomycin (BLM) complex exhibits high DNA cleavage efficiency, converting supercoiled Form I DNA (pBR322 or phix174) to Form II (nicked, relaxed circular); the present study may give an important clue to elucidate the fact that iron-bleomycin mediated double-strand DNA cleavage requires at least one molecule of oxygen (O2) over the amount required to form 'activated bleomycin."

Bleomycin↗

PubMedDate not supplied

Enhanced nucleophilicity and depressed electrophilicity of peroxide by zinc(II), aluminum(III) and lanthanum(III) ions.

The binuclear zinc(II) complex, [Zn2(HPTP)(CH3COO)]2+ was found highly active to cleave DNA (double-strand super-coiled DNA, pBR322 and phix174) in the presence of hydrogen peroxide. However, no TBARS (2-thiobarbituric acid reactive substance) formation was detected in a solution containing 2-deoxyribose (or 2'-deoxyguanosine, etc); where (HPTP) represents N,N,N'-N'-tetrakis(2-pyridylmethyl)-1,3-diamino-2-propanol. These facts imply that DNA cleavage reaction by the binuclear Zn(II)/H2O2 system should be due to a hydrolytic mechanism, which may be attributed to the enhanced nucleophilicity but depressed electrophilicity of the peroxide ion coordinated to the zinc(II) ion. DFT (density-functional theory) calculations on the peroxide adduct of monomeric zinc(II) have supported the above consideration. Similar DFT calculations on the peroxide adducts of the Al(III) and La(III) compounds have revealed that electrophilicity of the peroxide ion in these compounds is strongly reduced. This gives an important information to elucidate the fact that La3+ can enhance the growth of plants under certain conditions.

Aluminum↗

PubMedDate not supplied

Electronic property and reactivity of (hydroperoxo)metal compounds.

DFT calculations were done for the (hydroperoxo)metal complexes with eta1-coordination mode, where metal ions are Fe(III), Al(III), Cu(II) and Zn(II). Results shows that 1) the electron density at the two oxygen atoms of the hydroperoxide ion is highly dependent on the angle O-O-H in M-OOH species and the difference in electron density between the two oxygen atoms reaches a maximum at the angle O-O-H = 180 degrees, 2) total electron density at the two oxygen atoms of the peroxide ion increases by approach of methane to the (hydroperoxo)metal species in the cases of Fe(III) and Cu(II); on the other hand, significant decrease of the electron density on peroxide oxygen atoms was observed for the cases of Al(III) and Zn(II) compounds. These findings suggest that the (hydroperoxo)metal species acts as an electrophile in the former cases (M = Fe(III), Cu(II)) and as a nucleophile for the latter two compounds (M = Zn(II), Al(III)). The electrophilicity observed for the Fe(III) and Cu(II) complexes is attributed to the presence of unoccupied- or half-filled d-orbitals interacting with the hydroperoxide ion. 3) Two oxygen atoms of the (hydroperoxo)-compounds of Fe(III) and Cu(II) complexes exhibit quite different reactivity toward the substrate, such as methane. When methane approaches the oxygen atom which is coordinated to a metal ion, a strong decrease of electron density at the methane carbon atom occurs with concomitant increase of electron density at the peroxide oxygen atoms inducing its heterolytic O-O cleavage. When methane approaches the terminal oxygen atom, an oxidative coupling reaction occurs between peroxide ion and methane; at first a nucleophilic attack by the terminal electron-rich oxygen atom occurs at the carbon atom to induce C-O bond formation, and a subsequent oxidative electron transfer proceeds from substrate to the metal-peroxide species yielding CH3-OOH, CH3OH, or other oxidized products. These results clearly demonstrate that the (hydroperoxo)-metal compound itself is a rather stable compound, and activation of the peroxide ion is induced by interaction with the substrate, and the products obtained by the oxygenation reaction are dependent on the chemical property of the substrate, redox property of a metal ion, and stability of the compounds formed in the intermediate process.

Aluminum↗