A second protein L-isoaspartyl methyltransferase gene in Arabidopsis produces two transcripts whose products are sequestered in the nucleus.

The spontaneous and deleterious conversion of l-asparaginyl and l-aspartyl protein residues to l-iso-Asp or d-Asp occurs as proteins age and is accelerated under stressful conditions. Arabidopsis (Arabidopsis L. Heynh.

Evaluation of anti-prion activity of congo red and its derivatives in experimentally infected hamsters.

Among transmissible spongiform encephalopathies (TSE), particularly dreadful are the bovine spongiform encephalopathy (BSE), because of its epidemic character, and the new variant of Creutzfeldt-lakob disease (vCJD) in man, possibly related to BSE prion, through the intake of infected food. To treat TSE, many potentially therapeutic agents have been tested: some of them, among which is Congo Red (CAS 573-58-0, CR), delayed the onset of symptoms in scrapie-infected rodents, and some CR derivatives proved to be effective in vitro. The capacity of a synthesized CR derivative (CR-A) and of the aromatic central benzidine rings of CR (CR-B) to abrogate scrapie-induced disease in experimentally infected hamsters was assayed.

Early improvements in vision after fractionated stereotactic radiotherapy for primary optic nerve sheath meningioma.

Background And Purpose: To report on the efficacy and follow-up of 23 patients with primary optic nerve sheath meningioma (ONSM) with fractionated stereotactic conformal radiotherapy (SCRT).

Patients And Methods: Between 1996 and 2003, 23 patients ( = 23 eyes) with ONSM were treated. Indications for primary stereotactic radiotherapy were tumour progression documented by imaging or symptoms (loss of vision, pain).

Use and validation of novel snow samplers for hydrophobic, semi-volatile organic compounds (SVOCs).

Two novel gas-tight snow samplers (snow-can and snow-tube) are presented and the performance of the snow-can in a field trial was assessed. The methodology for the sampling, extraction and analysis of persistent organic pollutants (POPs) are detailed. These samplers allow the various components of a snow sample to be analysed separately; these included the meltwater (MW), particulate matter (GFF) and vapour in the headspace (HS).

Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors.

Purpose: To assess the long-term survival and prognostic factors associated with the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) and BVAM chemotherapy regimens followed by cranial radiotherapy in the treatment of primary central nervous system (CNS) non-Hodgkin lymphoma.

Methods And Materials: Since 1986, high-dose methotrexate (1.5 g/m(2)), cytarabine, vincristine, and carmustine have been used in the BVAM chemotherapy regimen for primary CNS non-Hodgkin's lymphoma, with one cycle of CHOD given before BVAM in patients View Article and Find Full Text PDF

A psychoncological study of lymphocyte subpopulations in relation to pleasure-related neurobiochemistry and sexual and spiritual profile to Rorschach's test in early or advanced cancer patients.

According to recent advances in psychoneuroimmunology concerning the neurobiochemistry of emotions, the pshychological status of cancer patients should be investigated in relation to the function of the psychoneurodocrine system, in an attempt to put into evidence possible cancer progression-related alterations, particularly those involving the dopaminergic pathways, which play a fundamental role in the perception of pleasure. In fact, the decreased capacity of feeling pleasure is one of the most frequent psychic symptoms occurring in cancer patients. Rorschach's test has been proven to be an appropriate psychological tool to investigate psychic condition including sexual and spiritual profiles.

Pharmacokinetics and distribution of sodium 3,4-diaminonaphthalene-1-sulfonate, a Congo Red derivative active in inhibiting PrP(res) replication.

Sodium 3,4-diaminonaphthalene-1-sulfonate (CRA) is a compound, synthesised by our group from Congo Red (CR), that is active in preventing the pathological conversion of normal prion protein (PrP). As the precise mechanisms controlling the ways in which prions are distributed and infect the brain and other organs are not fully understood, studying the pharmacokinetics of drugs that are active against prions may clarify their targets and their means of inhibiting prion infection. This paper describes the pharmacokinetics of CRA in plasma, spleen and brain after single or repeated intraperitoneal or subcutaneous administration, as determined by means of specific and sensitive fluorimetric HPLC.

Quantitative inter-specific chemical activity relationships of pesticides in the aquatic environment.

Inter-species correlations could be a useful tool for predicting toxicity and for establishing sensitivity ratios among species. In this paper, quantitative inter-specific chemical activity relationships (QICAR) for aquatic organisms were developed to verify if such an approach could be utilised for estimating toxicological data when no other information is available. Inter-specific toxicity relationships on fish, Daphnia and algae were performed for pesticides considering a large data set (more than 600 compounds) and grouping the data either on a functional (herbicides, fungicides and insecticides) or chemical class base.

In vitro evaluation of the anti-prionic activity of newly synthesized congo red derivatives.

"Transmissible Spongiform Encephalopathies" (TSE) are a group of degenerative progressive fatal disorders of the CNS, affecting both humans and animals. The main pathogenic event is the conversion of cellular prion protein from the normal, enzyme-sensitive (PrPsen), to the insoluble proteinase K-resistant isoform (PrPres). Since the new juvenile variant of Creutzfeldt-Jakob disease (vCJD) is probably due to the transmission of Bovine Spongiform Encephalopathy (BSE) prion protein to man, therapeutic and preventive compounds for animals and humans are urgently needed.

External beam radiotherapy in elderly patients with clinically localized prostate adenocarcinoma: age is not a problem.

The files of 183 elderly patients aged >70 years, with localized prostate cancer (T1-3, N0-X, M0), treated with radical external radiation therapy (ERT) from January 1992 to December 2001 at the Radiotherapy Department of the Istituto Nazionale Tumori of Milan, were reviewed. Median age was 75 years. ERT represented the sole treatment for 73 patients (39.

Congo red analogues as potential anti-prion agents.

'Transmissible Spongiform Encephalopathies' (TSE) are a group of degenerative, progressive and fatal disorders of CNS which affect both humans and animals, characterised by a long incubation time. The pathogenetic mechanism in TSE is the conversion of normal prion protein (PrP(sen)) to an altered protease resistant isoform (PrP(res)) that accumulates in amyloid deposits into the brain; therefore, PrP(res) is the primary target for therapeutic strategies. The discovery that the sulphonated azo dye Congo red (CR) is able to inhibit the replications of TSE agents and the accumulation of PrP(res) in animals and in scrapie infected mouse neuroblastoma cells induced us to designe molecules structurally related to CR (1a-f, 2f,g).

Synthesis of novel diazatricyclodecanes (DTDs). Effects of structural variation at the C3' allyl end and at the phenyl ring of the cinnamyl chain on mu-receptor affinity and opioid antinociception.

Two series of analogues of 9-propionyl-10-cinnamyl-9,10-diazatricyclo[4.2.1.

Development of a meningioma in a patient with acromegaly during octreotide treatment: are there any causal relationships?

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium.

Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial.

Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells.

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.

Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer.

Antiprolactinemic approach in the treatment of metastatic breast cancer: a phase II study of polyneuroendocrine therapy with LHRH-analogue, tamoxifen and the long-acting antiprolactinemic drug cabergoline.

Despite the well-demonstrated stimulatory role of prolactin (PRL) on breast cancer cell growth and the possible existence of a PRL-dependency in estrogen-independent mammary tumors, the therapeutic role of the antiprolactinemic drugs in the treatment of human breast cancer has still to be investigated and defined. Previous preliminary studies have already shown that the concomitant administration of antiprolactinemic agents may enhance the efficacy of cancer chemotherapy for breast carcinoma, whereas their impact on the efficacy of the endocrine therapy is still unknown. At present, the classic endocrine therapy for breast cancer consists of anti-estrogens plus LHRH-analogue.

Pesticide risk assessment in a lagoon ecosystem. Part II: effect assessment and risk characterization.

Ecotoxicological risk assessment for pesticides was performed on a coastal lagoon ecosystem (Orbetello lagoon, central Italy) according to the procedure described in the European technical guidance document (TGD) on risk assessment for new and existing substances. The procedure was applied to individual chemicals and to a mixture of chemicals with the same toxicological mode of action. Biomarker studies, measuring acetylcholinesterase (AchE) activity inhibition, were conducted on Zosterisessor ophiocephalus to compare the results of theoretical risk assessment with experimental measurements of ecotoxicological stress.

Pesticide risk assessment in a lagoon ecosystem. Part I: exposure assessment.

This work is the first step of a research project on pesticide risk assessment for a coastal lagoon ecosystem (Orbetello lagoon, central Italy). Pesticide exposure was evaluated by means of predictive and experimental approaches. Predicted environmental concentrations (PECs) for water and sediments were estimated using fugacity-based multimedia models.

[Growth hormone secretion in heart failure].

Growth hormone is a pituitary polypeptide hormone regulating growth in paediatric age as well as inducing anabolic actions directly or IGF-I mediated in adult age. Particularly, in many animals GH and IGF-I receptors were observed in cardiac myocyte membrane. GH modifies left ventricle structure and function.

Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas.

Background: The clinical evolution of anaplastic glioma (anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma) is variable. Previous studies merged patients with anaplastic glioma and the much more common glioblastoma multiforme. Therefore, the conclusions on prognostic factors reflected in part the consequences of an analysis in a heterogeneous population.

A clinical study of taxotere versus taxotere plus the antiprolactinemic agent bromocriptine in metastatic breast cancer pretreated with anthracyclines.

Prolactin (PRL) constitutes a growth factor for breast cancer cell proliferation and abnormally elevated blood concentrations of PRL are associated with poor prognosis and reduced efficacy of antitumor therapies in metastatic breast carcinoma. It has already been demonstrated that low-dose bromocriptine, an antiprolactinemic long-acting dopaminergic drug, normalizes PRL blood concentrations in metastatic breast cancer patients with abnormally elevated PRL levels. In addition, previous clinical studies have already demonstrated a lower efficacy of chemotherapy with taxotere in metastatic breast cancer, with persistent hyperprolactinemia.

Practice patterns for prostate cancer in nine central and northern Italy radiation oncology centers: a survey including 1759 patients treated during two decades (1980-1998).

Purpose: Prostate cancer patients in Italy are offered the choice of the full spectrum of possible treatment options for their disease, but the diffusion of the more recent technological refinements among the Radiation Oncology centers is not homogeneous and there is a need to establish a reference "historical" data source. This retrospective study describes the changing patterns in prostate cancer patient practice and the therapeutic results obtained in nine Radiation Oncology centers of Northern and Central Italy (five in Northern Italy and four in Central Italy).

Methods And Materials: A total of 1759 prostate cancer patients, radically treated in the nine radiotherapy (RT) centers between 1980 and 1998, made up the study population.

Determination of sodium 3,4-diaminonaphthalene-1-sulfonate, a Congo Red derivative, in plasma and brain of hamsters by high-performance liquid chromatography after solid-phase extraction and ultraviolet absorbance.

In the search for compounds with similar or greater activity than Congo Red (CR) in protecting normal prion protein from being converted into the pathological form, we have synthesized various compounds which derive from CR. One of these is the sodium 3,4-diaminonaphthalene-1-sulfonate (RCA) which has an activity similar to CR in preliminary experiments. This study describes a method to determine RCA in plasma and in brain tissue by high-performance liquid chromatography (HPLC), using a solid-phase extraction and UV detection.

Pre-irradiation semi-intensive chemotherapy with carboplatin and cyclophosphamide in malignant glioma: a phase II study.

We undertook a phase II trial in 17 patients with malignant glioma and large measurable disease to assess response rate and survival with pre-irradiation chemotherapy, using higher doses than standard, trying to improve the outcome. Patients characteristics were: male/female 10/7, age 49 (range 23-59), median Karnofsky index 90% (range 70-100), glioblastoma multiforme/anaplastic astrocytoma 14/3. Treatment consisted of 2 cycles of carboplatin 200 mg/m(2) days 1-3 (or AUC x 8, total dose) plus cyclophosphamide 1000 mg/m(2) days 1-3.

Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.

Purpose: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT).

Methods And Materials: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years).