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Biomedical subjects

M Ricci

Publications and source records attributed to M Ricci.

At least 91 records · Page 5Linked to original sources
PubMed1999

Pharmacokinetics and stability of the ch14.18-interleukin-2 fusion protein in mice.

The fusion protein formed from ch14.18 and interleukin-2 (ch14.18-IL-2), shown to exhibit antitumor efficacy in mouse models, consists of IL-2 genetically linked to each heavy chain of the ch14.18 chimeric anti-GD2 monoclonal antibody. The purpose of this study was to determine the pharmacokinetics of ch14.18-IL-2 in mice and assess its stability in murine serum. Following i.v. injection, the fusion protein was found to have a terminal half-life of 4.1 h. Detection of IL-2 following injection of the ch14.18-IL-2 fusion protein showed a similar half-life, indicating that the fusion protein prolongs the circulatory half-life of IL-2. Detection of human IgG1 following injection of ch14.18-IL-2 showed a terminal half-life of 26.9 h. These data suggested that the native fusion protein is being altered in vivo, resulting in a somewhat rapid loss of detectable IL-2, despite prolonged circulation of its immunoglobulin components. In vitro incubation of the ch14.18-IL-2 fusion protein in pooled mouse serum at 37 degrees C for 48 h resulted in a loss of its IL-2 component, as detected in enzyme-linked immunosorbent assay systems and in proliferation assays. Polyacrylamide gel electrophoresis and Western blot analysis of the fusion protein incubated in mouse serum at 37 degrees C indicated that the ch14.18-IL-2 is cleaved, resulting in a loss of the 67-kDa band (representing the IL-2 linked to the IgG1 heavy chain) and the detection of a band of more than 50 kDa, slightly heavier than the IgG1 heavy chain itself. This suggests that the fusion protein is being cleaved in vitro within the IL-2 portion of the molecule. These studies show that (1) ch14.18-IL-2 prolongs the circulatory half-life of IL-2 (compared to that of soluble IL-2) and (2) the in vivo clearance of the fusion protein occurs more rapidly than the clearance of the ch14.18 antibody itself, possibly reflecting in vivo cleavage within the IL-2 portion of the molecule, resulting in loss of IL-2 activity.

Animals↗
PubMed1999

Effects of low ozone-oxygen concentrations on the acetylcholine release at the mouse neuromuscular junction.

The use of a mixture of low concentrations of ozone (O3) with oxygen (O2) have been proved to be useful in different human pathological conditions. Owing to a lack of both pharmacological and epidemiological basic studies, the scientific consideration of this therapeutic potential is still inappropriate. Here, we started, from an electrophysiological point of view, a study on the possible effects of low O3 doses on the acetylcholine (ACh) release at the neuromuscular junction. Indeed, some experimental conditions indicate a positive effect either in maintaining cytosolic calcium (Ca2+) homeostasis or in increasing the efficacy of the intracellular antioxidant systems. Furthermore, a positive action on the kinetics of some antioxidant enzymes must be taken into account as a possible molecular mechanism in the regulation of the function of cellular homeostasis. Our data demonstrate a reduction of evoked ACh release in the mouse neuromuscular junction. O3 affects neither the spontaneous ACh release nor the kinetics of the ACh-receptor-channel complex. The results are compatible with a reduction of intracellular Ca2+ and proved a molecular action of O3.

Acetylcholine↗
PubMed1999

Dissemination of latent colon adenocarcinoma after laparoscopic cholecystectomy.

The seeding of neoplasms at trocar sites has been reported with increasing frequency. A case is presented of a 68 year-old woman with metastatic seeding of nondiagnosed colon cancer at the umbilical trocar site used for a laparoscopic cholecystectomy. Histopathological examination showed metastatic adenocarcinoma probably of gastrointestinal origin. A colonoscopy performed at the same time revealed a 2-cm lesion at the hepatic flexure which was shown histologically to be a differentiated adenocarcinoma. Diffuse peritoneal carcinomatosis was also found on computerised tomography. It is presumed that the primary colon cancer existed prior to cholecystectomy.

Adenocarcinoma↗
PubMed1999

cDNA, genomic cloning, and gene expression analysis of mouse PSP94 (prostate secretory protein of 94 amino acids).

The potential use of prostate secretory protein of 94 amino acids (PSP94) as a diagnostic biomarker or a therapeutic agent for prostate cancer has been reported. In order to establish an animal model to further elucidate on its biological role, we cloned the mouse PSP94 cDNA (approximately 500 bp) by reverse transcriptase-polymerase chain reaction (RT-PCR) and disclosed its genomic structure. The whole mouse PSP94 gene (approximately 23 kb) was amplified by long and accurate-PCR and also cloned by screening of a mouse embryo stem-cell genomic library. Computational and statistical analyses have demonstrated several highly conserved characteristics of PSP94 among different species. Comparison of PSP94 from human, two primates, pig, and rodents revealed that the most significant feature is that PSP94 is rich in cysteines (10% of the total sequence) and their positions are highly conserved. The three intron-four exon structure of the human PSP94 gene and the consensus sequence (....GT-intron-AG...) for mRNA splicing are also strongly conserved. A high divergence in cDNA sequence in the protein-coding region and also in the genomic sequence of PSP94 was also observed among these species. Comparing with alpha-globin, a typical evolutionally conserved gene, with the PSP94 gene, the rate of nonsynonymous changes per site per year (kN) is 2 to 6 times higher, indicating that PSP94 gene has been under far fewer evolutionary constraints than other genes and has a potential role as a species barrier in reproductive biology. In order to test this hypothesis, we investigated the gene expression of PSP94 and its tissue distribution in various rodent tissues by RT-PCR and in situ hybridization (ISH). Gene expression was found only in the prostate, suggesting that PSP94 is probably more tissue specific in the prostate of rodents than in mammals. The ISH analysis also revealed a prostate lobe-specific expression of the PSP94 gene in both mice and rats. It was strongly expressed in the lateral prostate, but the findings were negative in the dorsal and ventral lobe. Therefore, it is hypothesized that one of the primary functions of rodent PSP94, as a major prostate secretory protein, is related to reproductive biology.

Amino Acid Sequence↗
PubMed1999

Central venous access: accidental arterial puncture in a patient with right-sided aortic arch.

OBJECTIVE: To describe an unusual case of accidental insertion of a central line into an anomalous right-sided aortic arch. DESIGN: Case report, clinical. SETTINGS: Community hospital, university-affiliated. CONCLUSIONS: Intraoperative radioscopy, chest radiographs, and pressure transducer monitoring usually allow for the prompt recognition of the accidental insertion of venous catheters into the arterial system. However, in the presence of a right-sided aortic arch, a central line could be erroneously inserted into the arterial system and the radiologic findings can give the false impression of a correct placement in the superior vena cava.

Adult↗
PubMed1999

Specific enzyme-linked immunosorbent assays for quantitation of antibody-cytokine fusion proteins.

Preliminary testing has shown in vitro and in vivo that antitumor activity can be obtained with fusion proteins linking tumor-reactive monoclonal antibodies to cytokines, such as granulocyte-macrophage colony-stimulating factor or interleukin 2 (IL-2). Preclinical and clinical testing of these reagents requires their in vitro and in vivo quantitation and pharmacokinetic evaluation. We have focused on the detection of a fusion protein which links one human IL-2 molecule to the carboxy terminus of each heavy chain of the tumor-reactive human-mouse chimeric anti-GD2 antibody, ch14.18. We have developed enzyme-linked immunosorbent assays (ELISAs) to evaluate intact tumor-reactive fusion proteins. By these ELISAs we can reliably measure nanogram quantities of intact ch14.18-IL-2 fusion protein and distinguish the intact protein from its components (ch14.18 and IL-2) in buffer, mouse serum, and human serum with specificity and reproducibility. The measurement of intact ch14.18-IL-2 fusion protein is not confounded by free IL-2 or free ch14.18 when 100 ng or less of total immunoglobulin per ml is used during the assay procedure. Our results indicate that these ELISAs are suitable for preclinical and clinical testing and with slight modifications are applicable to the analysis of a variety of other fusion proteins.

Animals↗
PubMed1999

Open and laparoscopic cholecystectomy in acquired immunodeficiency syndrome: indications and results in fifty-three patients.

BACKGROUND: Although acute cholecystitis is one of the most common indications for abdominal surgery in patients with acquired immunodeficiency syndrome (AIDS), previous studies have reported disappointingly high morbidity and mortality among those patients who have undergone cholecystectomy. The aims of this study were to analyze the indications for and the outcome of cholecystectomy performed for acute cholecystitis in patients with AIDS. METHODS: We retrospectively reviewed the hospital charts of 53 patients with AIDS who underwent open or laparoscopic cholecystectomy from 1992 to 1997. Statistical analysis using the chi-square, Student's t, and Fisher exact tests was conducted to determine whether cause of cholecystitis, type of surgical approach, and CD4+ T-lymphocyte count influenced outcome. RESULTS: The clinical findings and imaging by ultrasonography were always reliable in establishing diagnosis and guiding treatment of acute cholecystitis. Open cholecystectomy was performed in 24 patients (45%). The procedure was begun laparoscopically in 29 patients (55%) and converted to open in 4 (14%). The pathologic findings showed acalculous cholecystitis in 19 patients (36%) and cholelithiasis in 32 (60%). Morbidity was 34% and mortality was 2%. Type of operative approach, cause of cholecystitis, and CD4+ T-lymphocyte count (greater or less than 50 cells/mm3) did not significantly affect morbidity and mortality. The length of hospital stay was significantly influenced by the CD4+ T-lymphocyte count. CONCLUSIONS: These findings suggest that in most patients with AIDS, laparoscopic or open cholecystectomy may be performed with significant but acceptable morbidity and low mortality.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Spread of hemoparasites in reptiles and amphibians in Italy].

Hemoparasites were harvested from 993 individuals belonging to 15 reptilian and 1 amphibian species, from various Italian localities. Hemogregarins were found in 10 reptilian species while a flagellate and microfilariae were found only in Tarentola mauritanica from Lampedusa. For each host species and place of origin the frequencies of hemogregarins are reported and discussed. Longitudinal studies with periodical thin smears were carried out on 5 Tarentola mauritanica, 4 Lacerta viridis, 26 Podarcis filfolensis, 10 Podarcis muralis, 38 Podarcis sicula, 8 Chalcides ocellatus. This material, whose study has not yet been completed, is made available by the author who strongly encourages further investigations on this subject.

Animals↗
PubMed1998

Self-care actions to manage fatigue among myasthenia gravis patients.

Fatigue is the most frequently reported symptom by myasthenia gravis (MG)patients. Despite the prevalence of fatigue, treatment protocols are lacking, thus patients are left to self-manage. The purpose of this study was to describe self-care actions used to manage fatigue among patients with MG. A national sample (N = 250) of MG patients responded to two structured instruments. The Fatigue Survey (FS), modified with permission of authors Hubsky and Sears; and the Myasthenia Gravis Fatigue Scale (MGFS). Both instruments were based on the concept of fatigue. Participants identified three major categories of self-managed actions: mental interventions (76%), physical interventions (78%) and rest/sleep (80%). A subset of the respondents (N = 36) reported using aerobic exercise to attempt to relieve fatigue which is usually contradicted with MG. No significant difference in fatigue scores was found between those reporting aerobic exercise to be helpful and those not finding exercise helpful. However, those utilizing aerobic exercise reported the highest functional status categories. A question arises as to whether aerobic exercise is performed by the least ill MG patients, or aerobic exercise improves functional status. When demographic and functional status variables were associated with fatigue scores and selfcare actions, only gender and functional status were significantly correlated with fatigue score. Effective self-care actions include stress reduction techniques, pacing all activities and increased rest and sleep. Further investigation into the role of aerobic exercise is indicated as a self-care action for MG fatigue.

Activities of Daily Living↗
PubMed1997

Long-term treatment of geropsychiatric depressed patients with venlafaxine.

Twenty-eight psychiatric patients older than 65 years with major depression with high probability of recurrence were enrolled in a 24-month open label clinical trial aimed at evaluating the long-term efficacy and safety of venlafaxine. All patients completed the acute phase of the study; 21 were responders and entered the follow-up period. During the continuation phase no relapse was observed. During the maintenance period, 20% of the patients had a single new recurrence. No significant side effects were observed. The results demonstrate that venlafaxine is both effective and safe in the long-term treatment of major depression in geropsychiatric patients.

Adrenergic Uptake Inhibitors↗
PubMed1997

[Bronchial asthma: pathogenetic mechanisms and genetic aspects].

At present there is a general consensus on the inflammatory nature of bronchial asthma. The main immunological features of the atopic state are represented by the ongoing expansion of Th2-like cells and production of IgE antibodies. IL-4 seems to represent the key factor for the differentiation of Th2-like cells, even though other cytokines have been recently proposed to play a some role. The possible genetic alterations which lead to the deregulated overexpression of IL-4 gene and of other genes of the same family in atopics are under active investigation. The existence of a polymorphism at level of IL-4 gene distal and proximal promoter has directly been shown. Even though IL-4 is required for the development and maintenance of atopic state, IL-5 certainly plays an essential role in the pathogenesis of bronchial inflammation in atopic, intrinsic and occupational asthma. On the basis of the findings emerged from new experimental models, it appears that there are different pathways by which T cell responses can develop bronchial eosinophilic inflammation but all the pathways have to lead to obligatory ongoing production of IL-5. The future research can be also addressed either to clarify the cytokines and/or other factors able to induce the differentiation and ongoing expansion of T cells prevalently producing IL-5, possibly involved in the pathogenesis of intrinsic asthma, either to understanding the nature of stimuli acting as etiologic factors. On the basis of the present acquisitions, IL-5 could represent the most important target of the new approaches to asthma therapy.

Animals↗