The potential role of magnetic resonance brain relaxometry in veterinary medicine: a preliminary study.

Magnetic Resonance (MR) is a non-invasive modality of choice for the evaluation of brain morphology, with superior performance as compared to other techniques. However, MR images are typically assessed qualitatively, thus relying on the experience of the involved radiologist. This may lead to errors of interpretation in the presence of subtle alterations and does not exploit the full potential of this technique as a quantitative diagnostic tool. To this end Magnetic Resonance Relaxometry (MRR), which is able to quantitively characterize the tissues under investigation through their relaxation rates, seems extremely promising. Many studies assessed the feasibility of relaxometry as a diagnostic tool in human brain disorders, with the most promising results obtained in the evaluation of neurodegenerative diseases and in the oncologic field. However, despite such extensive literature in human medicine, due to the lack of standardized protocols and the need of high-field MRI scanners, to date few studies have been performed on companion animals. In this work, first we describe relaxometry applications in human neuropathology and their possible extension to companion animals both in the experimental and clinical fields. Then, we present two experiments performed on a typical standard clinical scanner operating at 0.25 T to show that, despite the low field intensity, this technique may be promising even in the clinical setup. We tested the relaxometry protocol in a phantom study and then applied it to a real clinical case study. The results showed that this protocol used on a phantom led to a higher contrast, as compared to the standard approach. Furthermore, when applied to a real case study, this protocol revealed brain lesions undetected by the standard technique which were confirmed by a histopathological examination. These preliminary results are encouraging and support the development of this approach as an advanced diagnostic tool even in a clinical setting where low field MRI scanners are typically employed.

The Dim protein family: from structure to splicing.

The spliceosome is a dynamic macromolecular machine that catalyzes pre-mRNA splicing through a mechanism controlled by several accessory proteins, including the Dim proteins. The Dim protein family is composed of two classes, Dim1 and Dim2, which share a common thioredoxin-like fold. They were originally identified for their role in cell cycle progression and have been found to interact with Prp6, an essential component of the spliceosome, which forms the bridge of U4/U6.U5-tri-snRNP. In spite of their biological and structural similarities, Dim1 and Dim2 proteins differ in many aspects. Dim1 bears distinctive structural motifs responsible for its interaction with other spliceosome components. Dim2 forms homodimers and contains specific domains required for its interactions with partners. This originality suggests that although both proteins are involved in pre-mRNA splicing, they are likely to be involved in different biological pathways. In the present article we review the structure and function of the Dim proteins.

Structural role of the proline residues of the beta-hinge region of p13suc1 as revealed by site-directed mutagenesis and fluorescence studies.

Site-directed mutagenesis, gel filtration, and fluorescence spectroscopy approaches were used to study the molecular hinge mechanism involved in the beta-strand-exchanged dimer formation of the cyclin-dependent protein kinase regulatory subunit p13(suc1) from Schizosaccharomyces pombe. Single and double mutants of residues Pro-90 and Pro-92 (P90V, P92V, and P90V/P92V) were prepared and assayed. Substitution of Pro-90 prevented dimer formation by arm exchange. However, single point mutations did not affect the two-state unfolding transition of wild-type p13(suc1) at equilibrium (i.e., wild type, DeltaG degrees (0,un) = 7.38 +/- 0.35 kcal mol(-1), vs P90V, DeltaG degrees (0,un) = 6.71 +/- 0.18 kcal mol(-1)). On the contrary, the double mutant unfolded with a complex transition, and the reaction was best described by a three-state model (N <==> I <==> U). Resolution of the state-dependent (native vs denatured) intrinsic fluorescence decay amplitudes of p13(suc1) showed that with P90V/P92V these parameters were affected at [GuHCl] significantly less than with wild-type and single mutant proteins. Moreover, with the latter products, fluorescence quenching measurements at 1 M GuHCl revealed linear Stern-Volmer plots with quenching constants typical of tryptophan residues located in a native environment (1.6 M(-1) < K(SV) < 2.3 M(-1)). Dissimilarly, with P90V/P92V a significant deviation from linearity of the Stern-Volmer plot was obtained. Nonlinear least-squares analysis of these data resolved the significant contribution of highly solvent-accessible emitting species (K(SV) = 26 M(-1)) consistent with large exposure of the tryptophan residues. These results are compatible with the existence of an intermediate unfolding state of the double mutation product. Thus, while single residue substitution studies give support to the primary role of Pro-90 in the p13(suc1) dimer formation by domain swapping, double residue substitution studies indicate the important role of the conserved repeat, Pro-x-Pro, for the proper beta-strand spatial organization and stability.

[Out-of-the-hospital care for terminal cancer patients. Clinical and organizational features. Our experience]. / Assistenza extraospedaliera al paziente oncologico terminale. Aspetti clinico-organizzativi. Nostra esperienza.

Home care for terminal oncological patients is, in Italy and in many other highly developed countries, a rapidly expanding part of the health system. At the time of writing it would appear to be the most valid response to the mounting economic and social demands of the population. The present paper has two purposes: 1) to propose an integrated home care operating model for the cancer patient that comprises various operating stages: a) recruitment of patients on the basis of the seriousness of the cancer, life expectancy and socioeconomic conditions of the family; b) interdisciplinary planning of a personalized care project; c) implementation of an integrated care programme at the home of the patient; d) periodic control of the project team; e) periodic professional courses for health personnel; 2) to illustrate our specific clinical expertise in the sector, in 16 months of activity (October 94-February 96) during which we handled on a home basis 27 cancer patients at an advanced stage of the disease; specifically, we describe the main internal-oncological and palliative type problems encountered during the home care period; 3) finally, to highlight in terms of cost/benefit ratio the economic advantages of home compared to the traditional hospitalization care model.

Serum ostase in the follow-up of breast cancer patients.

The present study was carried out on 152 patients divided into three groups: A) 73 underwent radical surgery for breast carcinoma without signs of metastases; B) 31 patients with radiologic and scintigraphic evidence of bone metastases originating from malignant mammary neoplasia (14 with only one and 17 with two or more localizations); C) 48 affected by simple mammary cysts. No patients had a previous history of primary or secondary bone pathologies or renal, hepatic or endocrine ones. Besides this, no patient took drugs influencing the metabolic turnover of the bony tissue in the three months preceding the study. After surgery all patients underwent standard clinical and laboratory follow-up, the latter including, every 3 months, the evaluation of serum CA 15.3, CA 27.29 MCA, and ostase. The ostase cut-off, obtained by the statistical elaboration of the serum values of the 48 patients with benign mammary cysts and the 73 disease free patients, was 17 microg./L. The mean concentration in the three groups and two subgroups was: 13.76 microg./L (patients without metastases), 31.84 (patients with metastases), 18.4 (limited bony metastases), 40.04 (diffused bony metastases) and 5.36 (mammary cists). The diagnostic sensitivity of ostase proved superior to that of CA 15.3 (84% vs 75%) except when considering the subgroup with limited metastases (71.4% vs 72.7%), while the specificity was similar (around 78%). CA 27.29 and MCA were not useful as markers of metastasis. In a longitudinal-perspective study it was possible periodically to test these markers in 13 patients, at first, disease free and then with signs of bone progression evidence by skeletal scintigraphy. In 11 of these patients ostase and CA 15.3 showed increased values, an average 136 and 131 days respectively, before instrumental evidence of progression. None of the 13 patients, at the time of bone progression diagnosis, showed clinical, laboratory or instrumental signs of disease in other organs. The precocity of the serum increase of ostase could have a triple role: 1) accomplishment of a closer follow-up in patients at "high risk" of bone disease; 2) aid in the interpretation "in a neoplastic sense" of an "uncertain image of hypercaptation"; 3) accomplishment of a supporting or specific oncology treatment at an earlier stage which may be of some advantage as regards quality of life.

[Prognostic factors in operated breast carcinoma]. / Fattori prognostici del carcinoma mammario operato.

The traditional prognostic factors (tumour size, lymph node involvement, receptor status) have now been shown to have limits in terms of prognostic definition. These limits may be partially overcome when parameters exist to determine the extent of tumour biological aggression and the patient's degree of immune response. It is important to clarify these links because they may lead to more precise indications regarding the prognosis and choice of therapy, above all in cases of breast cancer operated with no lymph node involvement. Breast carcinoma is often surrounded by inflammatory cells showing host and tumour interaction. The aim of this study was to evaluate the prognostic value of lymphocyte infiltration in operated breast cancer. The degree of lymphocyte infiltration observed in 56 breast cancer patients was compared with other prognostic factors (tumour size, lymph node status, histological variants, necrotic areas and desmoplastic reaction). This preliminary study allowed the authors to examine the degree of peritumoral lymphocyte density as an important predictive index of overall survival in patients with breast cancer and N-.