Homologous expression of the nrdF gene of Corynebacterium ammoniagenes strain ATCC 6872 generates a manganese-metallocofactor (R2F) and a stable tyrosyl radical (Y˙) involved in ribonucleotide reduction.

Ribonucleotide reduction, the unique step in the pathway to DNA synthesis, is catalyzed by enzymes via radical-dependent redox chemistry involving an array of diverse metallocofactors. The nucleotide reduction gene (nrdF) encoding the metallocofactor containing small subunit (R2F) of the Corynebacterium ammoniagenes ribonucleotide reductase was reintroduced into strain C. ammoniagenes ATCC 6872.

Gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones: synthesis, characterization, cytotoxicity, and interaction with ribonucleotide reductase.

A series of gallium(III) and iron(III) complexes with five different 4N-substituted alpha-N-heterocyclic thiosemicarbazones, viz., 2-acetylpyridine N,N-dimethylthiosemicarbazone (1), 2-acetylpyridine N-pyrrolidinylthiosemicarbazone (2), acetylpyrazine N,N-dimethylthiosemicarbazone (3), acetylpyrazine N-pyrrolidinylthiosemicarbazone (4), and acetylpyrazine N-piperidinylthiosemicarbazone (5), with the general formula [GaLCl2] (HL = 1 and 2) and [ML2][Y] (M = Ga, HL = 1-5, Y = PF6; M = Fe, HL = 1-5, Y = FeCl4 and PF6) were synthesized and characterized by elemental analysis, a number of spectroscopic methods (NMR, IR, UV-vis), mass spectrometry, and X-ray crystallography. The in vitro antitumor potency was studied in two human cancer cell lines (41M and SK-BR-3).

PELDOR study on the tyrosyl radicals in the R2 protein of mouse ribonucleotide reductase.

Pulse electron-electron double resonance (PELDOR) has been employed to measure the distance between the putative tyrosyl radicals in the two halves of the R2 subunit from mouse ribonucleotide reductase. The results provide experimental evidence that the active, tyrosyl radical containing mouse R2 subunit forms a homodimeric form in solution. The distance between the two tyrosyl radicals present in the dimer was determined to be 3.

An advanced EPR stopped-flow apparatus based on a dielectric ring resonator.

A novel EPR stopped-flow accessory is described which allows time-dependent cw-EPR measurements of rate constants of reactions involving paramagnetic species after rapid mixing of two liquid reagents. The EPR stopped-flow design represents a state-of-the-art, computer controlled fluid driving system, a miniresonant EPR structure with an integrated small ball mixer, and a stopping valve. The X-band EPR detection system is an improved version of that reported by Sienkiewicz et al.

Osteosarcoma in children: long-term functional analysis.

Multimodal, limb-saving therapy is the treatment of choice in children with osteosarcoma. However, few data are available on long-term functional problems and disabilities in surviving patients. Seventy-eight children treated for Stage II-B osteosarcoma who were treated between 1970 and 1997 were evaluated.

Examples of high-frequency EPR studies in bioinorganic chemistry.

Low-temperature EPR spectroscopy with frequencies between 95 and 345 GHz and magnetic fields up to 12 T has been used to study metal sites in proteins or inorganic complexes and free radicals. The high-field EPR method was used to resolve g-value anisotropy by separating it from overlapping hyperfine couplings. The presence of hydrogen bonding interactions to the tyrosyl radical oxygens in ribonucleotide reductases were detected.

Stability and transmetallation of the magnetic resonance contrast agent MnDPDP measured by EPR.

MnDPDP [manganese(II) N, N'-dipyridoxylethylenediamine- N, N'-diacetate-5,5'-bis(phosphate)] is the active component of Teslascan, a contrast medium for magnetic resonance imaging of the liver. It has previously been shown that MnDPDP is rapidly dephosphorylated to the monophosphate MnDPMP and the non-phosphorylated MnPLED, and that all these substances are rapidly transmetallated to the corresponding Zn complexes. In the present study we used EPR at 9 and 230 GHz to show that no free Mn(2+) ions can be detected in the product or in a mixture of MnDPDP and human serum.

Anticancer drug sensitivity and expression of multidrug resistance markers in early passage human sarcomas.

We have established new human sarcoma lines and examined their sensitivity to common antitumor drugs and expression of putative multidrug resistance (MDR) proteins. Eighty-two sarcoma samples were transplanted in nude mice. Fourteen of these sarcomas were established as tumor cell lines.

[Are expanded tumor resection and reconstruction of soft tissue sarcoma justified by recurrence rate and survival time?].

The outcome of two groups of patients treated for soft tissue sarcoma either by a "limited resection" or by a radical procedure, including reconstructive techniques to vessels and soft tissues coverage, was compared. The latter group showed a higher rate of R0 resections, prolonged time to recurrence and a significantly decreased recurrence rate. Also, fewer patients developed distant metastases.

Expression of the mdr1 gene in bone and soft tissue sarcomas of adult patients.

The expression of the mdr1 gene was evaluated at the RNA level by northern and slot blot analysis, and at the protein level by immunohistochemistry, in a total of 29 bone and 32 soft tissue sarcomas. All patients, mainly adults, had not received previous chemotherapy. Of the tumours investigated, 69% were mdr1-positive.

The development of osteosarcoma in four-fold selected group of patients.

Patients with osteosarcoma have been submitted to four-fold selection using parameters previously shown to be associated factors. These are sex, age at onset, haptoglobins and histological type. Further data have been added to the final resulting sequence of patients.

[The value of computed tomography in monitoring the preoperative chemotherapy of osteosarcoma].

Computed tomography was performed in 45 patients with osteosarcomas before and after preoperative chemotherapy. Changes of bone alterations, intramedullary tumour spread and the size of soft tissue masses are computer tomographic criteria for tumour response after chemotherapy. The computed tomography decision of responder or non-responder was correct in 37/45 patients.

[Malignant fibrous histiocytoma of soft tissue. Possibilities and limitations of computed tomography].

Computed tomography was performed in 27 patients with confirmed malignant fibrous histiocytoma of the soft tissue. Compared with the CT results obtained in other tumours of the soft tissues. CT accuracy in malignant fibrous histiocytoma was only 74%.

[Malignant bone tumors--possibilities and limits of surgical treatment].

Surgical treatment of patients for malignant bone tumours, its possibilities and limits, is expounded in this paper on the basis of results and experience obtained from more than 330 cases. Reference is made to adjuvant chemotherapy which today is an indispensable component of complex treatment at least for osteosarcoma and Ewing's sarcoma. Described are ablative procedures, ranging from amputation to hemicorporectomy, and limb-saving operations, including implantation of tumour-specific endoprotheses which has assumed growing importance in recent years.

CT evaluation of osseous tumors.

Computed tomography was performed on 153 patients with histologically proved bone tumors. CT has been found to be important for demonstrating the extent of the lesion, in aiding decisions about the operative approach, especially in tumors of the shoulder girdle and pelvis, and also for planning of localized surgery to maintain extremities. CT is of limited value in determining the nature of tumors.

[Diagnostic imaging of peripheral soft tissue tumors with special reference to computed tomography].

The further development of modern therapeutical procedures in the treatment of soft tissue tumors requires an improvement of radiological diagnostics. The diagnostic values of X-rays, angiography, sonography and computed tomography is estimated critically. The results of own CT examinations in 120 patients with soft tissue tumors and of 50 ultrasound examinations show the importance of these methods in the extent diagnosis of soft tissue tumors.