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Biomedical subjects

G Valentini

Publications and source records attributed to G Valentini.

At least 91 records · Page 5Linked to original sources
PubMed1996

Anti-topoisomerase-I and clinical findings in systemic sclerosis (scleroderma).

The relationship between anti-topoisomerase-I antibodies and clinical findings was studied in 191 patients with definite systemic sclerosis. This was done by performing ELISA to detect antibodies to recombinant topoisomerase-I. Antibodies to topoisomerase-I were found in 72 patients (37%) with systemic sclerosis, which is a higher percentage than reported in most previous reports on a large unselected population. In 43 patients the presence of antibodies to recombinant topoisomerase-I was confirmed using both the immunodiffusion method and ELISA, with similar results. When classified into diffuse versus limited disease, a significant difference in antibody prevalence was demonstrated (P < 0.005), thus indicating that anti-topoisomerase-I antibody detection with ELISA may assist in early identification of systemic sclerosis subtypes.

Autoantibodies↗
PubMed1996

[Cardiopathy in systemic sclerosis].

Cardiac involvement is quite frequent in systemic sclerosis (SSc). From a pathophysiologic point of view, one must differentiate a primary scleroderma heart disease due to pericardial and/or myocardial and/or small coronary intramyocardial vessel involvement from heart disease secondary to either pulmonary interstitial or vascular involvement (pulmonal cor) or to kidney disease (hypertensive myocardial disease). A significant difference emerges when the prevalence of clinically and standard ECG detected cardiac involvement in SSc patients is compared with that registered at autopsy. In the last years, however, Holter ECG, echocardiography, perfusional scintigraphy and ventriculography have reduced such gap, a preclinical scleroderma heart disease being detected by such techniques in quite a high percentage of SSc patients. Asymptomatic SSc patients may be found to present small pericardial effusions and/or either fixed (fibrosis) or reversible (vascular disease) or both types thallium defects or a defective cardiac functional reserve. Both clinically evident scleroderma heart disease and ventricular arrhythmias have a poor prognostic significance. Therefore, a complete cardiological work-up must be periodically carried out in SSc patients. Scleroderma heart disease has long been considered a condition difficult to treat. The detection of diastolic abnormalities and of diastolic failure in SSc patients make us able to understand the therapeutic failure of inotropic agents. Recently, captopril has been shown to improve cardiac function in SSc. It might act either on vascular disease or on fibrosis by affecting the remodelling process of the myocardial wall.

Cardiomyopathies↗
PubMed1995

Crystallization and preliminary X-ray analysis of pyruvate kinase type I from Escherichia coli.

Crystals of the fructose-l,6-bisphosphate-dependent pyruvate kinase from Escherichia coli have been grown using the hanging-drop vapour-diffusion technique. The space group was found to be C222(1) with cell dimensions a = 76.8, b = 247.5, c = 132.6 A. Diffraction data to 3.0 A resolution have been recorded and the enzyme molecular symmetry analysed through inspection of the self-rotation function. The crystallized protein is in the allosterically inactive T state.

Journal Article↗
PubMed1995

Non-dominant dorsal-prefrontal activation during chess problem solution evidenced by single photon emission computerized tomography (SPECT).

Expert chess players can recall meaningful chess positions with extraordinary precision in comparison with inexperienced players. We hypothesized, therefore, that their mental performance during chess deliberation could be an appropriate target for single photon emission computerized tomography (SPECT) studies. We studied cerebral activation with 1110 MBq 99mTc-Bicisate SPECT in five expert male chess players during mental solution of a complex chess problem. Region of interest (ROI) analysis, in comparison with average weighted cerebellar counts, showed activation by 10% or more, of the non dominant prefrontal area (right in four dominant right handed players, left in one dominant left handed player) and by 2-6% in the non-dominant middle temporal areas. Maximum variability of ROI analysis versus cerebellar counts in test/retest evaluation is in our laboratory, as in others, 1.5%. Our results are in agreement with neuropsychological studies suggesting that the non-dominant hemisphere is specialized for chess skill, and show that non-dominant prefrontal and temporal lobe activation during chess deliberation can be detected by SPECT.

Adult↗
PubMed1995

Crystal structure of Escherichia coli pyruvate kinase type I: molecular basis of the allosteric transition.

BACKGROUND: Pyruvate kinase (PK) plays a major role in the regulation of glycolysis. Its catalytic activity is controlled by the substrate phosphoenolpyruvate and by one or more allosteric effectors. The crystal structures of the non-allosteric PKs from cat and rabbit muscle are known. We have determined the three-dimensional structure of the allosteric type I PK from Escherichia coli, in order to study the mechanism of allosteric regulation. RESULTS: The 2.5 A resolution crystal structure of the unligated type I PK in the inactive T-state shows that each subunit of the homotetrameric enzyme comprises a (beta/alpha)8-barrel domain, a flexible beta-barrel domain and a C-terminal domain. The allosteric and active sites are located at the domain interfaces. Comparison of the T-state E. coli PK with the non-allosteric muscle enzyme, which is thought to adopt a conformation similar to the active R-state, reveals differences in the orientations of the beta-barrel and C-terminal domains of each subunit, which are rotated by 17 degrees and 15 degrees, respectively. Moreover, the relative orientation of the four subunits differs by about 16 degrees in the two enzymes. Highly conserved residues at the subunit interfaces couple these movements to conformational changes in the substrate and allosteric effector binding sites. The subunit rotations observed in the T-state PK induce a shift in loop 6 of the (beta/alpha)8-barrel domain, leading to a distortion of the phosphoenolpyruvate-binding site accounting for the low substrate affinity of the T-state enzyme. CONCLUSIONS: Our results suggest that allosteric control of PK is accomplished through remarkable domain and subunit rotations. On transition from the T- to the R-state all 12 domains of the functional tetramer modify their relative orientations. These concerted motions are the molecular basis of the coupling between the active centre and the allosteric site.

Allosteric Regulation↗
PubMed1995

Efficacy of photodynamic therapy against doxorubicin-resistant murine tumors.

Photodynamic therapy (PDT) is a relatively new cancer treatment modality that employs light excitation of a photosensitizer to yield cytotoxic oxygen-related species. In the present study we explored whether PDT would have therapeutic effect against doxorubicin-resistant murine tumors. We compared the efficacy of PDT with aluminium disulphonated phthalocyanine (A1S2Pc) and laser light on the doxorubicin-sensitive murine tumors, B16 melanoma (B16), L1210 leukemia (L1210), P388 lymphoma (P388) and the corresponding doxorubicin-resistant lines (B16/Dx, L1210/Dx and P388/Dx). Mice bearing L1210-L1210/Dx, P388-P388/Dx and B16-B16/Dx, were treated with 5 mg/kg of A1S2Pc and laser light (100 mW/cm2 x 10 min of exposure) or with doxorubicin (10 or 12 mg/kg i.v.). The results show that PDT is active versus all tumors while doxorubicin is effective only against the three sensitive tumor lines (L1210, P388 and B16). These observations suggest that PDT might be a beneficial alternative treatment for drug-resistant tumors.

Animals↗
PubMed1995

Study of porphyrin fluorescence in tissue samples of tumour-bearing mice.

A time-gated fluorescence-imaging technique was applied to study the distribution of sensitizer in porphyrin-treated tumour-bearing mice. The animals were administered with either haematoporphyrin derivative (HpD) or Photofrin and sacrificed 4 or 12 h later. Fluorescence images were acquired from tumour, skin, muscle, fat, brain, lymph node, bowel and bone of both treated and untreated mice. The results obtained with HpD and Photofrin are similar. In images acquired 30 ns after excitation a bright exogenous fluorescence allows clear detection of the tumour. Nevertheless, the images show that porphyrins localize with different concentrations in all the examined tissues except the brain. Moreover, an appreciable long-living endogenous emission was observed in the bone.

Animals↗
PubMed1995

delta-Aminolevulinic acid induced fluorescence in tumour-bearing mice.

The potential of protoporphyrin IX fluorescence induced by the systemic administration of delta-aminolevulinic acid (ALA) for the detection of tumours was tested in three different murine models (MS-2 fibrosarcoma, L1210 leukaemia, and Lewis lung carcinoma). Time-gated fluorescence images were acquired up to 4 h after the intraperitoneal injection of ALA (200 mg (kg body mass (BM))-1). For comparison images were acquired also after the administration of 25 mg (kg BM)-1 of haematoporphyrin derivative. The latter drug was characterized by better localization in the tumour area, leading to higher fluorescence contrast between neoplastic mass and surrounding healthy tissue, and consequently was preferable for tumour diagnosis in all the models under study.

Aminolevulinic Acid↗
PubMed1995

Affinity labelling of the catalytic and allosteric ATP binding sites on pyruvate kinase type I from Escherichia coli.

The allosterically regulated pyruvate kinase type I (PKI) from E. coli was inactivated by the ATP analog 2',3'-dialdehyde ATP (o-ATP) with a Ki of 3.6 mM. ATP and phosphoenolpyruvate protected the enzyme activity while the allosteric activator fructose 1,6-bisphosphate enhanced the rate of inactivation. Incubation with o-ATP, followed by reduction of the formed Schiff bases with radioactive sodium borohydride, was employed to determine the ATP binding sites of PKI. After tryptic digestion, the purification of the labelled peptides and the sequence analysis allowed to identify four modified lysyl residues, namely Lys173, Lys175, Lys272, and Lys317 of the known DNA-deduced sequence of PKI. The close lysines 173 and 175 reacted with o-ATP in a mutually exclusive way and accounted together for 53% of the recovered radioactivity, the rest being distributed on Lys272 (31%) and Lys317 (16%). When fitted on the available three-dimensional structure of muscle pyruvate kinase, the position of the modified lysines defines both the catalytic and the allosteric ATP binding sites on PKI.

Adenosine Triphosphate↗
PubMed1994

Efficacy of L-propionylcarnitine treatment in patients with left ventricular dysfunction.

The effect of L-propionylcarnitine on patients with left ventricular dysfunction (EF < 45%) NYHA class II, symptomatic despite therapy with digitalis and diuretics was evaluated in a phase II parallel, double-blind, randomized, placebo-controlled study. Fifty patients (28 men and 22 women) aged 37-70 years received 1.5 g of L-propionylcarnitine or placebo on a random basis as oral treatment for 6 months. At baseline, during a 7 day placebo run-in period, and during the 6-month treatment bicycle exercise test, M-B mode and Doppler echocardiography, and clinical evaluation (clinical score) were repeatedly performed. The analysis of variance for repeated measurements showed a statistically significant difference (P < 0.01) in the mean value of exercise time between the treatments over the period of the study. There was a final increase of 0.36 min in the placebo group, 1.4 min in the treated group and a minor production of lactate during exercise in the treated group. Left ventricular shortening fraction and left ventricular ejection fraction showed a significant increase in the L-propionylcarnitine group (respectively P < 0.01 and P < 0.0001) whereas no difference was apparent in the placebo group. Stroke volume index and cardiac index showed significant increments in the treated group (P < 0.05) and systemic vascular resistance was lowered (P < 0.05). No haemodynamic variations were observed in the placebo group, and the clinical score showed a significant improvement in the L-propionylcarnitine treated group. In conclusion, L-propionylcarnitine treatment was shown to improve patient symptomatology and effort tolerance.

Adult↗
PubMed1994

Antitumor immunity induced by photodynamic therapy with aluminum disulfonated phthalocyanines and laser light.

Photodynamic therapy (PDT) is systemic administration of tumor localizing photosensitizers and subsequent irradiation with light of the appropriate wavelength. The combination of drug uptake in malignant tissues and selective delivery of laser-generated light provides effective therapy, with efficient tumor cytotoxicity and minimal normal tissue damage. There have been few studies of the effects of photoactivated photosensitizers on the host immune response. Since immunity is important in the control of tumor growth and spread, we have examined, in our laboratory, the effects of photoactivated phthalocyanines on the antitumor immune response. Immunosuppressed and normal mice bearing the MS-2 fibrosarcoma treated with 5 mg/kg of aluminum disulfonated phthalocyanine (AIS2Pc) and then the tumor mass exposed to laser light (100 mW/cm2 x 10 min) or treated with surgical excision of the tumor survived indefinitely, with no difference between the different groups. The survivors, tumor-free 100 days after the treatment modalities described above, were rechallenged with the parental MS-2. Some groups of surviving animals were immunosuppressed with cyclophosphamide before the injection of the tumor. Resistance to rechallenge was evidenced only in normal surviving animals cured by PDT, while the immunodepressed surviving animals and animals cured by surgery died of tumor. Finally, mice, cured by PDT and tumor-free, rechallenged with L1210 and P388 murine leukemias did not survive. These results suggest that a potential and specific 'antitumor immunity' is induced by PDT with photoactivated AIS2Pc.

Animals↗
PubMed1994

Absorption spectrum of hematoporphyrin derivative in vivo in a murine tumor model.

Time-resolved reflectance was used to measure the absorption spectrum of hematoporphyrin derivative (HpD) in vivo in a murine tumor model. Reflectance measurements were performed in the 600-640 nm range on mice bearing the L1210 leukemia. Then the animals were administered 25 mg/kg body weight of HpD intraperitoneally. One hour later the reflectance measurements were repeated. Fitting of the data using the diffusion theory allowed assessment of the absorption coefficient before and after the administration. As a difference between the latter and the former data, the in vivo absorption spectrum of HpD was evaluated. Maximum absorption was measured at 620-625 nm. Similar spectral behavior was obtained for HpD in solution in the presence of low-density lipoproteins.

Animals↗
PubMed1994

[Respiratory exchange during laparoscopic and laparotomic cholecystectomy].

The utility of laparoscopic cholecystectomy in reducing postoperative pain and patient's hospital discharge is already known. Nevertheless peritoneal gas insufflation required by surgical procedure can modify respiratory homeostasis during general anesthesia. The aim of this study was to evaluate the effect of laparoscopic cholecystectomy on pulmonary dead spaces and alveolar gas exchange during inhalation anesthesia compared with traditional laparotomic cholecystectomy. With the approval of Hospital Ethical Committee, thirty-one patients undergoing isoflurane general anesthesia for laparoscopic (CL-S, n = 16) and open (CL-T, n = 15) cholecystectomy were prospectively evaluated in order to asses modifications in physiological (VDphy/VT), anatomical (VDan/VT) and alveolar (VDalv/VT) dead space to tidal volume ratio, arterial to end-tidal carbon dioxide partial pressure difference [P(a-Et)CO2] and alveolar to arterial oxygen partial pressure difference (A-aDO2). Patients, 21-64 years-old, ASA I-II, had no cardiopulmonary diseases. The CL-S group required peritoneal insufflation of carbon dioxide with an intraabdominal pressure (IAP) of about 10-14 mmHg and antitrendelenburg positioning (15-20 degree). Expired gas measurements and arterial blood gas sample for pulmonary dead spaces and arterial to alveolar CO2 and O2 gradient calculation were performed 20 min after a steady state condition. VDphy/VT, VDalv/VT, P(a-Et)CO2 and A-aDO2 increased significantly in the CL-S compared to the CL-T group (p < 0.05). No differences were found in the VDan/VT. These results can be explained by analteration of the ventilation to perfusion ratio (VA/Q) with an increase of high VA/Q regions due to the antitrendelenburg positioning with a redistribution of blood flow towards basal zones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A pilot clinical trial of postoperative adjuvant intraperitoneal cisplatin, 5-fluorouracil, 6S-leucovorin and interferon alpha 2b in patients with resected gastric cancer.

AIMS AND BACKGROUND: The study was performed to assess the toxicity and impact on relapse pattern of postoperative intraperitoneal cisplatin, 5-fluorouracil, leucovorin and interferon therapy as adjuvant treatment for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2 N1-2; T3-4 N any Mo). PATIENTS AND METHODS: Starting 14 to 21 days after potentially curative resection of primary gastric cancers, 22 patients were given intraperitoneal cisplatin, 60 mg/m2; 5-fluorouracil, 1000 mg/m2; 6S-leucovorin, 250 mg/m2; interferon alpha 2b, 10 MU/m2; every other week for six times. RESULTS: After a median follow-up of 24 months, 63% of patients were alive and free of disease. Eight patients had recurred; five had an intraabdominal component, and 3 had extraabdominal failure. Toxicity was mild: no grade III-IV WHO toxicity was observed. CONCLUSIONS: Intraperitoneal cisplatin, 5-fluorouracil, 6S-leucovorin and interferon is a tolerable therapy in the postoperative setting for patients with resected gastric cancer. These data make this approach interesting for the development of new programs of adjuvant therapy of high-risk gastric cancer.

Adult↗
PubMed1993

The complement system and systemic sclerosis.

Serum concentrations of the various complement components including the classical and the alternative pathways were determined in 58 control healthy subjects and 80 patients with systemic sclerosis (SSC). The mean concentrations of C1q, C2, C5, C6, C7, C9, and factor B were significantly increased in the SSC patients in comparison to controls, while the increases were not significant for C3 and C8. C4 was an exception in that the mean levels were found to be decreased, with 18 patients having levels < 65% of the mean normal value. Properdin was also found to be decreased, but not significantly. We found a similarity between the pattern of serum complement component concentrations in SSC patients and patients with primary biliary cirrhosis, two disorders frequently associated in the same patients. The significance of complement component patterns in these diseases is discussed.

Complement Activation↗
PubMed1993

Time-gated fluorescence imaging for the diagnosis of tumors in a murine model.

A system for time-gated fluorescence imaging was used to perform measurements on tumor-bearing mice treated with hematoporphyrin derivative (HpD). The aim of the study was to define the potential of this technique in the diagnosis of tumors by taking advantage of the long fluorescence lifetime of the exogenous dye with respect to the decay times of the natural fluorescence. After the administration of three different drug doses (5, 10 and 25 mg/kg body weight), fluorescence images were acquired at various uptake times (from 2 h to 10 d), to determine the best instrumental conditions and experimental procedure for the detection of tumors in the murine model considered. The optimal fluorescence contrast between the tumor area and the surrounding healthy tissue was found at 12 h after the administration of either 5 or 10 mg/kg HpD and was anticipated at 8 h for the highest drug dose. In this optimum condition, the tumor region could be identified even after the injection of 5 mg/kg HpD. A better fluorescence contrast was always obtained in 15 ns-delayed images with respect to synchronous ones.

Animals↗
PubMed1993

Cardiac involvement in rheumatoid arthritis: an echocardiographic study.

Thirty-nine consecutive patients with rheumatoid arthritis (RA) and 40 control subjects were studied by echocardiography in order to assess the incidence of cardiac involvement in this disease. The occurrence of anatomic lesions in our series was lower than that observed in other studies. No differences in mean values of left and right ventricular diastolic function indexes obtained by Doppler echocardiography were found between patients and controls. However, in 26% of patients with RA, left ventricular abnormalities probably secondary to myocardial fibrosis were observed.

Arthritis, Rheumatoid↗