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D Rossi

Publications and source records attributed to D Rossi.

At least 19 recordsLinked to original sources
PubMed2000

ATP-induced activation of expressed RyR3 at low free calcium.

Ca(2+) channel properties of the mink ryanodine receptor type 3 (RyR3), expressed in HEK293 cells, were studied in planar lipid bilayers to which RyR3 rich membrane fragments had been fused. RyR3 channels were not active at resting levels of Ca(2+)(free) but were gated by an additional 1 mM ATP, exhibiting long open times. The second major finding was the absence of channel inactivation at millimolar Ca(2+)(free). Insertion of a myc tag at the N-terminus of RyR3 did not affect the channel properties. As to skeletal muscle, the observed type 3 channel properties appear physiologically meaningful by assisting type 1 channels in calcium release.

Adenosine Triphosphate↗
PubMed2000

Steroid and cyclophosphamide in IgA nephropathy.

BACKGROUND: IgA nephropathy is associated with a wide spectrum of possible lesions. Therefore, different responses to anti-inflammatory or immunosuppressive therapies should be expected with acute inflammatory changes, which are predominantly reversible, and with prevalently sclerotic lesions. METHODS: The effects of a combined schedule of prednisone and cyclophosphamide was analysed in the specific subset of IgA nephropathy patients with acute inflammatory histologic changes associated with haematuria and proteinuria. Two groups of patients, with similar histologic lesions and clinical presentation, were considered. The first group (12 patients) was treated within 1 week after renal biopsy; starting with three pulses of methylprednisolone (1 g) followed by oral prednisone (0.8 mg/kg body weight for 2 weeks, 0.6 mg/kg for another 2 weeks, 0.4 mg/kg for an additional 4 weeks, then slowly tapered by 5 mg each month until discontinuation) and 1.5 mg/kg cyclophosphamide for 2 months. A second sample of eight untreated patients served as a control group. Treated and untreated patients had diffuse mesangial proliferation with florid crescents (8-60% in treated and 10-40% in untreated patients) with mild degree of glomerular sclerosis and interstitial changes. Basal creatinine (167 micromol/l, range 79-371 vs 132 micromol/l, range 79-256) and proteinuria (3.0 g/24 h, 1.0-4.9 vs 3.3 g/24 h, 1.0-13.7) were not statistically different between treated and untreated patients respectively. Nine treated and six untreated patients were hypertensive. Blood pressure treatment did not include ACE-inhibitors. RESULTS: Untreated patients' 5-year renal survival, as assessed by the Kaplan-Meier method, was found to be significantly lower than treated patients (37.5 vs 91.6%, log-rank P=0.01 and Breslow test P=0.008; relative risk to reach the endpoint of a 100% increase in serum creatinine=3.58, P=0.03). CONCLUSION: This short course of therapy with prednisone and cyclophosphamide has been effective in a subset of IgA nephropathy patients with florid glomerular changes and major urinary abnormalities, turning off phlogistic activity and preventing subsequent progression toward renal failure.

Adolescent↗
PubMed2000

The biology of chemokines and their receptors.

During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection (1). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation (2), B (3), and T (4) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis (5). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines' biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.

Animals↗
PubMed1999

Spatially segregated control of Ca2+ release in developing skeletal muscle of mice.

1. Confocal laser scanning microscopy was used to monitor Ca2+ signals in primary-cultured myotubes, prepared from forelimbs of wild-type or ryanodine receptor type 3 (RyR3) knockout mice. Myotubes loaded with the acetoxymethyl ester (AM) form of fluo-3 were imaged at rest or under whole-cell patch clamp. 2. Discrete Ca2+ release events were detected in intact wild-type and RyR3-knockout myotubes. They showed almost no difference in amplitude and width, but were substantially different in duration. In wild-type myotubes (660 events, 57 cells) the amplitude was 1.27 (0.85, 1.97) (median (25 %, 75 %)) units of resting fluorescence, the full width at half-magnitude (FWHM) was 1.4 (0.9, 2.3) microm, and the full duration at half-magnitude (FDHM) was 25.3 (9.6, 51.7) ms. In RyR3-knockout myotubes (655 events, 83 cells) the amplitude was 1.30 (0.84, 2.08), FWHM was 1.63 (1.02, 2.66) microm, and FDHM was 43.6 (23.6, 76.9) ms. 3. Depolarization under voltage clamp of both wild-type and RyR3-knockout myotubes produced substantial Ca2+ release devoid of discrete Ca2+ events. Discrete events were still present but occurred without correlation with the applied pulse, largely at locations where the pulse did not elicit release. 4. The local correspondence between voltage control and absence of discrete events implies that the functional interaction with voltage sensors suppresses the mechanism that activates discrete events. Because it applies whether RyR3 is present or not, it is this exclusion by voltage of other control mechanisms, rather than isoform composition, that primarily determines the absence of discrete Ca2+ events in adult mammalian muscle.

Animals↗
PubMed1999

psi(SO2NH) transition state isosteres of peptides. Synthesis and bioactivity of sulfonamido pseudopeptides related to carnosine.

This paper reports the synthesis of tauryl dipeptides related to carnosine. In particular H-Tau-His-OH (5), H-Tau-His(pi-Me)-OH (6) and H-Tau-His(tau-Me)-OH (9) are described. The enzyme carnosinase has been isolated from pig kidney and after purification has been used to test the stability and the inhibitory activity of the three new analogues. H-Tau-His-OH (5) and H-Tau-His(tau-Me)-OH (9) were found to possess weak inhibitory properties towards carnosinase, while H-Tau-His(pi-Me)-OH (6) proved to be devoid of any significant activity. All the three sulfonamido pseudopeptides 5, 6 and 9 show stability to carnosinase activity.

Carnosine↗
PubMed1999

[Urinary complications of Erdheim-Chester disease].

BACKGROUND: Erdeheim-Chester disease is an uncommon histiocytosis. Fifty-nine cases have been reported in the literature. Bone lesions are usually inaugural followed by multiorgan involvement combining bone disease, orbital infiltration, diabetes insipidis and retroperitoneal infiltration. CASE REPORT: A 53-year-old man had Erdheim-Chester disease which progressed over 11 years. The patient developed extrinsic obstruction of the upper urinary tract. This unusual complication of Erdheim-Chester disease raised a difficult therapeutic problem as percutaneous drainage was impossible. The patient was treated with an endoprothesis allowing urine derivation. Surgical ureterolysis was avoided. DISCUSSION: Data in the literature favor use of minimally invasive endourological treatment for patients with urinary tract complications of Erdheim-Chester disease.

Histiocytosis↗
PubMed1999

Identification of a chicken "C" chemokine related to lymphotactin.

In this study we describe the isolation and characterization of a new chicken (Gallus gallus) chemokine. This molecule belongs to the C or gamma-chemokine family and is related to the mouse and human lymphotactin (Lptn). Mouse and human Lptn are distinguished from alpha and beta chemokines by the absence of two cysteines (Cys 1 and 3) that form a disulfide bridge; the novel chicken chemokine shows the same cysteine pattern, but replaces a long carboxy-terminal tail found in the other Lptn proteins with a short extension rich in Arg residues. The 1-kb mRNA is mainly expressed in spleen, although weaker signals have been detected in liver and colon. It is interesting to note that the chicken chemokine seems to preferentially induce the migration of spleen B cells over T cells or B cells from the bursa of Fabricius.

Amino Acid Sequence↗
PubMed1999

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase II study.

BACKGROUND: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule. PATIENTS AND METHODS: Thirty-six untreated patients with stage IIIB IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on day 1,8, and 15, followed by one week of rest. RESULTS: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%-57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4-23) and the median survival time 11.8 months (range 1-24). World Health Organization (WHO) grade 3-4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity. CONCLUSIONS: This regimen appears to be active and to have a favourable toxicity profile.

Adult↗
PubMed1999

[What is the role of the correspondence of free PSA/total PSA in the staging of local prostate cancer? Series of 50 radical prostatectomy cases].

OBJECTIVE: To refine the pretreatment staging of localized prostate cancers. MATERIAL AND METHOD: Prospective study on 50 total prostatectomy specimens from men with apparently prostate-confined adenocarcinoma. Preoperative assay of the free PSA/total PSA ratio and analysis of this ratio according to the presence of capsular effraction, capsular invasion and positive margins. RESULTS: Significant difference of this ratio according to the presence or absence of capsular effraction (13.2% versus 18.9%), capsular invasion (12.4% versus 17.5%) and positive margins (11.6% versus 16.3%). CONCLUSION: The free PSA/total PSA ratio can be useful for staging of prostate cancer, but this needs to be confirmed by a large-scale prospective study.

Adenocarcinoma↗
PubMed1999

[Conformal radiotherapy].

Conformal radiotherapy is a new irradiation technique made possible by technological improvements, especially progress in imaging and 3D dosimetry. By conforming the volume irradiated as closely as possible to the clinical anatomical target volume, conformal radiotherapy is designed to deliver a higher dose to the tumour volume, while more effectively sparing the adjacent tissues from the adverse effects of irradiation. Conformal radiotherapy may therefore constitute a progress comparable to the contribution of high-energy radiotherapy in the 1960s or the impact of computer-assisted dosimetry in the 1970s. Evaluation of the results, definition of its indications, standardisation of practices, and study of the impact of dose escalation require further studies in the field of prostate cancer, as the superiority of this new technique over conventional radiotherapy has not been formally established due to the limited follow-up.

Humans↗
PubMed1999

[The use of bronchial fibroscopy for difficult intubations in maxillofacial surgery].

BACKGROUND: Evaluation of difficulties and modalities of tracheal intubation in maxillofacial surgery. METHODS DESIGN: retrospective study. SETTING: maxillofacial operation room. 2152 patients who underwent elective maxillofacial surgery during a five-year time, from 1994 to 1998. Indications and alternative modalities of tracheal intubation through fiberoptic bronchoscope in eight patients (0.37%) with preoperatively evaluated difficult intubation due to temporomandibular ankylosis (3 patients), burns sequelae (1 patient), craniofacial congenital malformations (2 patients), unstables fractures of the cervical spine (2 patients), are discussed. Fiberoptic bronchoscope was used through nasotracheal route under topical nasal and laryngeal anaesthesia, combined with appropriate benzoanalgesia, in order to maintain spontaneous breathing. Proper positioning of tracheal tube was directly checked by fiberoptic bronchoscope, through visualization of the tracheal carina. RESULTS: In seven patients tracheal intubation was easily performed without complications in less than 20 minutes. In the eight patients the time spent was 35 minutes, due to important nasal bleeding, which caused a change of the nostril. CONCLUSION: Among the alternative methods of elective tracheal intubation, previously evaluated as difficult or impossible using conventional laryngoscopy, the use of fiberoptic bronchoscope seems to be safest and easiest to use, although not the cheapest.

Adult↗
PubMed1998

In situ activation of the type 2 ryanodine receptor in pancreatic beta cells requires cAMP-dependent phosphorylation.

Molecular mechanisms that regulate in situ activation of ryanodine receptors (RY) in different cells are poorly understood. Here we demonstrate that caffeine (10 mM) released Ca2+ from the endoplasmic reticulum (ER) in the form of small spikes in only 14% of cultured fura-2 loaded beta cells from ob/ob mice. Surprisingly, when forskolin, an activator of adenylyl cyclase was present, caffeine induced larger Ca2+ spikes in as many as 60% of the cells. Forskolin or the phosphodiesterase-resistant PKA activator Sp-cAMPS alone did not release Ca2+ from ER. 4-Chloro-3-ethylphenol (4-CEP), an agent that activates RYs in other cell systems, released Ca2+ from ER, giving rise to a slow and small increase in [Ca2+]i in beta cells. Prior exposure of cells to forskolin or caffeine (5 mM) qualitatively altered Ca2+ release by 4-CEP, giving rise to Ca2+ spikes. In glucose-stimulated beta cells forskolin induced Ca2+ spikes that were enhanced by 3,9-dimethylxanthine, an activator of RYs. Analysis of RNA from islets and insulin-secreting betaTC-3-cells by RNase protection assay, using type-specific RY probes, revealed low-level expression of mRNA for the type 2 isoform of the receptor (RY2). We conclude that in situ activation of RY2 in beta cells requires cAMP-dependent phosphorylation, a process that recruits the receptor in a functionally operative form.

Animals↗
PubMed1998

Genomic structure and chromosomal location of the human TGFbeta-receptor interacting protein-1 (TRIP-1) gene to 1p34.1.

The human TRIP-1 (transforming growth factor-beta (TGBbeta)-receptor interacting protein-1) cDNA encodes a protein able to associate specifically with the type II TGFbeta receptor. It is phosphorylated on serine and threonine by this receptor kinase which makes it a strong candidate as part of the TGFbeta signal transduction pathway. We have isolated the genomic sequence of TRIP-1 and found that the complete coding region is organised into 11 exons ranging from 39 to 397 bp and spanning approximately 9 kb of genomic DNA. The 5' flanking region lacks a TATA box but is GC-rich, suggesting that it is a constitutively expressed gene which is in agreement with its wide pattern of expression. Fluorescence in situ hybridisation mapped the TRIP-1 gene to chromosome 1p34.1 whereas a pseudogene is located on chromosome 7q32.

Chromosomes, Human, Pair 1↗
PubMed1998

Prostaglandins stimulate calcium-dependent glutamate release in astrocytes.

Astrocytes in the brain form an intimately associated network with neurons. They respond to neuronal activity and synaptically released glutamate by raising intracellular calcium concentration ([Ca2+]i), which could represent the start of back-signalling to neurons. Here we show that coactivation of the AMPA/kainate and metabotropic glutamate receptors (mGluRs) on astrocytes stimulates these cells to release glutamate through a Ca2+-dependent process mediated by prostaglandins. Pharmacological inhibition of prostaglandin synthesis prevents glutamate release, whereas application of prostaglandins (in particular PGE2) mimics and occludes the releasing action of GluR agonists. PGE2 promotes Ca2+-dependent glutamate release from cultured astrocytes and also from acute brain slices under conditions that suppress neuronal exocytotic release. When applied to the CA1 hippocampal region, PGE2 induces increases in [Ca2+]i both in astrocytes and in neurons. The [Ca2+]i increase in neurons is mediated by glutamate released from astrocytes, because it is abolished by GluR antagonists. Our results reveal a new pathway of regulated transmitter release from astrocytes and outline the existence of an integrated glutamatergic cross-talk between neurons and astrocytes in situ that may play critical roles in synaptic plasticity and in neurotoxicity.

Animals↗
PubMed1998

Different doses of pamidronate in patients with painful osteolytic bone metastases.

Cancer patients with painful osteolytic bone metastases who had failed initial treatment with hormones and/or chemotherapy were each randomized to receive one of three pamidronate doses as outpatients: 45, 60, 90 mg given every 3 weeks for 12 weeks. Seventy patients were enrolled in this study, for a total of 265 infusions. There were 64 patients who completed 12 weeks of therapy. Forty-eight patients took nonsteroidal antinflammatory drugs, while 22 patients received morphine before pamidronate treatment. A reduction in bone pain and mobility scores was observed in all three different dose groups: in 11 of 23 patients (47%) at 45 mg; in 12 of 24 patients (50%) at 60 mg; and in 16 of 23 patients (69%) at 90 mg. However, while for patients receiving pamidronate at 90 mg median changes in pain and mobility were statistically significant at the 6th week, for patients receiving 45 mg they were not significant until the 12th week and for patients receiving 60 mg, until the 9th week. In weeks 0-6, the daily consumption of analgesics was reduced in 3 patients in the 45-mg arm, in 4 patients in the 60-mg arm, and in 7 patients in the 90-mg arm. In weeks 7-12, the daily consumption of analgesics was reduced in 8 patients receiving 45 mg, in 8 patients receiving 60 mg, and in 7 patients receiving 90 mg. No significant toxicity was recorded. In 2 patients (45 and 90 mg) fever (> 38 degrees C) and myalgia were observed after the first administration. In conclusion, our results seem to confirm the utility of higher doses of pamidronate in patients with painful bone metastases, because of the faster symptom relief achieved.

Adult↗
PubMed1998

Patch-clamp, ion-sensing, and glutamate-sensing techniques to study glutamate transport in isolated retinal glial cells.

We have described how a combination of electrical, ion-sensing, and glutamate-sensing techniques has advanced our understanding of glutamate uptake into isolated salamander retinal glial cells. The next steps in understanding glutamate transport will inevitably depend strongly on molecular biological methods, as described elsewhere in this book, but will also require more detailed study of transporters in their normal environment, perhaps by using patch-clamping or imaging techniques to study cells in situ.

ATP-Binding Cassette Transporters↗