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Biomedical subjects

G Falcone

Publications and source records attributed to G Falcone.

At least 55 records · Page 3Linked to original sources
PubMed1995

2-aryl-3-phenylamino-4,5-dihydro-2H-benz[g]indazoles with antiarrhythmic and local anaesthetic activities.

The synthesis of novel 2-aryl-3-phenylamino-4,5-dihydro-2H-benz[g]indazoles 4a-f, starting from N-phenyl-3,4-dihydro-1(2H)-oxonaphthalene-2-carbothioamide and the proper arylhydrazines, is described. Title compounds were evaluated for antiinflammatory, analgesic, antipyretic, antiarrhythmic, hypotensive, local anaesthetic and platelet antiaggregating activities; some of them showed an appreciable antiarrhythmic activity in rats and a good level of infiltration anaesthesia in mice.

Analgesics↗
PubMed1995

[Widened forwarding total laryngectomy ("squared laryngectomy"). Hints of surgical techniques and personal experience].

Primitive T4 laryngeal neoplasms with anterior invasion and neoplasm recurring after partial and subtotal intervention often invade the soft prelaryngeal tissues and in these cases the neoplastic illness can be no longer be controlled be "organ surgery". The widened forwarding total laryngectomy, "squared" or "carrè" laryngectomy according to some Authors of French School, is a surgical procedure not "on an organ" but "in an area" or "region" which proposes to delete, in one step, the larynx, the bone hyoid, the fasciae and the prelaryngeal muscles, the thyroid gland and, if necessary, a more or less large quantity of anterior cervical skin. If the removal involves a vast cutaneous area, it is necessary to mend the loss of substance by wrapping around a miocutaneous flap of pectoralis mayor muscle. In the last five years, 4 male patients, between 48 and 73 years, were treated with widened forwarding total laryngectomy. They were all carriers of epidermoid laryngeal carcinomas with various degrees of differentation: primitive in one patients, recidivist after performance of partial (cordectomy) and subtotal (two Labayle) surgery in the other three patients. In the only case of T4 primitive laryngeal neoplasm it was necessary to carry out a functional neck dissection bilaterally. Loss of substance always required the use of a miocutaneous flap of pectoralis mayor muscle except in one patient in which the removal of the prelaryngeal tissues was limited and therefore it was possible to make a direct seam. We always completely removed the thyroid gland, the prelaryngeal muscular system and skin of the preceding stomy (in the Labayle) sparing, on the other hand, the hyoid bone. Only one patient, who died due to recurrence a year after surgery, underwent complemental percutaneous radiotherapy. At present, three patients are alive and NED: one after 5 years, the others are in excellent conditions although the follow-up is still brief. According to our experience, we can affirm that in selected cases, after an accurate general evaluation of the patient (exclusion of distant metastases, preparation from a metabolic and psychological point of view) a widened forwarding total laryngectomy is a valid procedure since surgery (together with other complementary therapies), is still today the best treatment in forms with anterior evolution.

Aged↗
PubMed1994

Epstein-Barr virus-transformed human B lymphocytes produce natural antibodies to histones.

To study the mechanism(s) responsible for the appearance of Epstein-Barr virus (EBV)-induced anti-histone autoantibodies, peripheral blood B lymphocytes from healthy donors were infected with EBV and the resulting lymphoblastoid cell lines were tested for secretion of antibodies reacting with histones. It was found that EBV-transformed cells produce IgM antibody reactive with histones and that the frequency of EBV-inducible circulating B lymphocytes that produce antibodies to histones is at least 10(-5). Moreover, in cultures of tonsillar lymphoid cells, the enrichment in CD5+ B lymphocytes increases the percentage of EBV-transformed cultures making anti-histone IgM antibodies. EBV may therefore, also in vivo, induce natural anti-histone antibody by polyclonal B-cell activation without any requirement of antigen to trigger antibody response.

Antigens, CD↗
PubMed1992

Epstein-Barr virus-transformed B lymphocytes produce low molecular mass molecules with autocrine growth factor and competence factor activity.

A human Epstein-Barr virus (EBV)-positive lymphoblastoid B cell line, named BA-D10-4, produces a factor of a molecular mass less than 10 kDa that promotes cell proliferation of both BA-D10-4 cells and other human T or B lymphoid cell lines, either EBV-positive or -negative. The factor synergizes with higher molecular mass autocrine growth factors and makes both BA-D10-4 cells and B cell lines from Burkitt's lymphoma, but not cells from T cell leukemia, more responsive to interleukin-1 and interleukin-6. Therefore, this low molecular mass factor seems to be an autocrine growth factor per se and to have the characteristics of a competence factor.

B-Lymphocytes↗
PubMed1992

Antibodies to histones in infectious mononucleosis.

A polyspecific human monoclonal (auto)antibody, isolated from a patient in the acute phase of infectious mononucleosis, was found to react with all subfractions (H1, H2A, H2B, H3 and H4) of histones. This finding prompted us to study the occurrence of antibodies to histones in sera of patients with infectious mononucleosis. It was found that IgM binding to histones was detectable both in control and patient sera; however, sera from patients showed binding values of IgM antibodies to histones significantly higher than those of healthy controls; moreover, both in control and patient groups anti-histone IgM activity was found to correlate with serum IgM concentration. These findings suggest that anti-histone IgM antibodies belong to the class of antibodies defined as "natural antibodies" and that their increase during infectious mononucleosis is due to Epstein-Barr virus-induced polyclonal B cell activation.

Antibodies, Monoclonal↗
PubMed1992

Detection of an idiotope on a human monoclonal autoantibody by monoclonal anti-idiotypic antibody and its relationship to Epstein-Barr virus-induced autoimmunity.

We have recently described a human IgM monoclonal antibody (mAb), reactive with both self antigens, i.e., cytoskeleton filaments and smooth muscle, and Epstein-Barr virus (EBV)-induced nuclear antigen (EBNA), produced by EBV-transformed B lymphocytes isolated from a patient with infectious mononucleosis (IM). In order to achieve higher antibody secretion in culture supernatant, the mAb-producer cells were fused with ouabain-resistant mouse myeloma cells and a stable human-mouse heterohybrid, coded HY 5488, producing up to 80 micrograms/ml IgM mAb, was isolated after 4 cloning procedures. Purified HY 5844 mAb was used to immunize mice for the production of a murine anti-idiotypic mAb, which was used to probe the expression of the idiotope of HY 5488 mAb (Id 5488) in sera of IM patients and normal controls by ELISA. It was found that Id 5488 is expressed both in IM patients and normal controls, and that Id 5488 expression is significantly higher in IM patients' sera; furthermore, in IM sera a statistically significant correlation between Id 5488 expression and anti-cytoskeleton and anti-smooth muscle autoantibodies was found. It is suggested that at least part of EBV-induced IgM autoantibodies appearing during IM are secreted by B lymphocytes programmed to the production of "natural antibodies" bearing Id 5488-like idiotopes.

Animals↗
PubMed1992

Transformation of NIH3T3 cells by Rous sarcoma virus occurs with high efficiency in the absence of proviral rearrangements or amplification.

NIH3T3 cells could be transformed by a mammaltropic strain of Rous sarcoma virus (RSV) with an efficiency 10(3) times greater than that observed in Balb/c 3T3 cells or other mammalian cell lines and almost identical to that of chick embryo fibroblasts. In infected NIH3T3 cells a single, properly integrated, provirus was sufficient to induce focus formation; moreover, kinase activity of pp60v-src and tyrosine phosphorylation of cellular proteins could be detected very soon after infection in the majority of cells. On the other hand, in transformed foci from RSV-infected Balb/c 3T3 cells both rearrangements and amplification of proviral sequences were frequently detected. Accordingly, expression of pp60v-src and ensuing tyrosine phosphorylation of cellular proteins occurred, at high levels, only in a minority of the infected cells. Furthermore, by using a murine retrovirus carrying the v-src oncogene and an independent selectable marker, we found that Balb/c 3T3 cells were transformed with a 100-fold lower efficiency than NIH3T3 cells, yet the majority of infected untransformed Balb/c 3T3 cells expressed active pp60v-src. These findings are consistent with the existence in most mammalian cell lines of a major restriction to v-src-induced transformation, operating at the level of proviral expression, that is apparently absent in NIH3T3 cells.

3T3 Cells↗
PubMed1992

[Left ventricular false tendon: the most frequent cause of "innocent" murmur in childhood?].

BACKGROUND: The left ventricular false tendon (FT) is an anomalous fibrous or fibromuscular band stretching across the left ventricle. The false tendons extend from the septum to the left ventricular free wall or, more rarely, from the septum to a papillary muscle. The association between FT and innocent cardiac murmur has been pointed out. The aim of the present study was to assess the incidence of FTs in children with a murmur classified as innocent. METHODS: Two groups of subjects were selected. Group A consisted of 253 children with: 1) systolic ejection murmur; 2) normal electrocardiogram and 3) absence of clinical data suggesting cardiac disease. Group B consisted of 240 children clinically free of cardiac disease, and without any cardiac murmur. A FT was diagnosed by means of 2D echocardiogram whenever a linear band stretching across the left ventricular chamber was evident in at least two sections. RESULTS: One hundred and sixty-one children of group A (63.6%) reflected a left ventricular FT; only in 3 patients out of 161 the FT was associated with a small ventricular septal defect, whereas in 158 children the FT was the only abnormal finding. A normal echocardiogram was observed in 71 children (28.1%) of group A; whereas in 21 patients (8.3%) a congenital heart disease was diagnosed. In group B, only 33 subjects (13.8%) had a FT. The different incidence of FT in the two groups (63.6% versus 13.8%) was statistically significant (p less than 0.01). CONCLUSIONS: The study shows that about two thirds of children with innocent heart murmur reflect a left ventricular FT. Furthermore, FT is far more common in subjects with innocent cardiac murmur than in normal subjects. The relationship between FT and murmur thus appears very likely, although not definitely proven.

Adolescent↗
PubMed1991

Transcription of muscle-specific genes is repressed by reactivation of pp60v-src in postmitotic quail myotubes.

Quail myogenic cells infected with temperature sensitive (ts) mutants of Rous sarcoma virus (RSV) exhibit a temperature-dependent transformation and block of differentiation. When the cells are allowed to differentiate at the restrictive temperature (41 degrees C) and then shifted back to the permissive temperature (35 degrees C), a sharp reduction in the accumulation of muscle-specific mRNAs is observed, following reactivation of the transforming protein pp60v-src. A kinetic analysis of this down-regulation reveals that the reduction in the accumulation of muscle-specific transcripts occurs fairly rapidly within 6 to 20 h after the shift back, depending on the mRNA analyzed. Studies on transcription of endogenous muscle-specific genes and a transfected chloramphenicol acetyltransferase reporter gene under the control of muscle-specific promoters, at the different temperatures, suggest that the oncogene exerts its control mainly at the transcriptional level. On the contrary, transcription of the CMD1 gene, the avian homolog of the mouse muscle regulatory MyoD gene, is not significantly affected by the oncogene both in proliferating myoblasts and in myotubes shifted back to 35 degrees C. These findings are consistent with the conclusion that v-src blocks myogenesis by controlling transcription of muscle-specific genes independently of cell proliferation. Furthermore, they suggest the existence of an alternative pathway, not requiring the silencing of CMD1 transcription, through which the oncogene exerts its effect.

Actins↗
PubMed1991

Therapeutic efficacy and renal effects of cefonicid in the treatment of difficult urinary tract infections.

UNLABELLED: EFFICACY, renal effects and nephrotoxicity of the cephalosporin cefonicid (CEF) were evaluated in 11 adult patients with urinary tract infection and varying renal function (creatinine cl 19-161 ml/min, mean 75). CEF was administered i.m. for 7 days at a daily dose adjusted to renal function of the patients. EFFICACY: At the 4th day and at the end of the treatment urine cultures were negative in all cases; a recurrence of the infection was observed in 4 patients 10 days after completion of therapy. Renal effects and nephrotoxicity: CEF neither modified plasma creatinine, urea, uric acid and their renal clearances nor glomerular filtration rate. Only the urinary enzyme activity of alanine aminopeptidase increased slightly at the end of the therapy. It returned to basal values in the post-treatment period. Urinary enzyme activities of gamma-glutamyltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and lysozyme were unmodified during and after treatment with CEF. These results indicate that CEF is an effective antimicrobial agent which does not influence renal function, nor cause nephrotoxic effects.

Adult↗
PubMed1990

[Complications of gastroduodenal peptic ulcers].

The paper reports that the introduction of H2-antagonist histamine drugs has led to the present drastic contraction of surgical therapy and complications related to gastroduodenal peptic ulcers. Following a brief discussion of the diagnostics of the various complications of the disease, the surgical urgency is then underlined and case studies are presented (A. Vinci). Thirty-seven hemorrhagic ulcers are reported, 32 of which were completely treated with somatostatin and blood transfusions and 5 were operated for gastrosection during hemorrhage; 70 acute gastroduodenal perforations and 8 blocked pyloroduodenal stenoses are also reported. The surgical approach used for each type of complication is discussed, underlining the end-result to be attained in relation to the patient's future. It is stressed, however, that the surgeon's main goal must be to save the patient's life using the simplest and most efficacious method available.

Duodenal Ulcer↗
PubMed1990

[Modern view of the pathogenesis and therapy of gastroduodenal peptic ulcer].

After a wide analysis of peptic gastroduodenal ulcer medical therapy, before and after the era of cimetidine, the Authors, after a brief account of the Anatomy and Physiology of the stomach, examine surgical therapy, from the end of the last century till now. After giving the results of the surgical cases of one of them (A. Vinci), including 500 operations, from 1955 till now, almost all with gastric resection, without vagotomy, the Authors point out that today, in the era of cimetidine, surgical therapy has considerably diminished and is reserved only for the complications of pathological cases (perforation, hemorrhage, closed duodenum stenosis), and for those cases which don't respond to antisecretory pharmacological therapy. They also emphasize, that nowadays, in spite of the cooperation among gastroenterologists, gastroscopists and surgeons, the etiopathogenesis of peptic ulcer isn't clear yet, and they conclude by saying that our lack of knowledge of its origin and natural evolution, doesn't guarantee a definitive cure, although the therapy with cimetidine and similar medicines, according to the Authors' personal experiences and opinion, must be continued for the patient's entire life.

Anti-Ulcer Agents↗
PubMed1990

Differential control of muscle-specific gene expression specified by src and myc oncogenes in myogenic cells.

Myogenic cells can be transformed in vitro by the introduction of several exogenous viral oncogenes. Transformed myoblasts are prevented from terminal differentiation into myotubes by the continuous expression of oncogenes such as myc and src, chosen as prototypes of nuclear and cytoplasmic oncogenes. A comparative analysis of the relationship between transformation and differentiation in myoblasts and cells belonging to other lineages has led to the proposal that terminal differentiation of myc-transformed quail myoblasts is indirectly prevented by the loss of growth control and that myc-bearing cells remain susceptible to growth regulation by interaction with adjacent normal cells. On the contrary, the src oncogene appears to affect expression of the myogenic programme via a direct mechanism, independent from abnormal growth control. There is increasing evidence for the existence of master regulatory genes that govern and influence muscle development in vivo and myogenic differentiation in vitro. Expression of cytoplasmic oncogenes such as src, ras and polyoma middle T in the mouse myogenic cell line, C2, results in inhibition of biochemical differentiation and a marked down-regulation of the MyoD1 and myogenin genes.

Animals↗
PubMed1989

Interaction with normal cells suppresses the transformed phenotype of v-myc-transformed quail muscle cells.

We have analyzed mixed cultures of normal mammalian fibroblastic cells and transformed quail myoblasts to investigate whether the presence of an excess of normal cells could suppress the phenotype of transformed quail cells. In such mixed cultures, only v-myc-transformed cells were growth-arrested, whereas v-src-transformed myoblasts were essentially unaffected. Growth arrest appeared to reflect reversion from the transformed state, including re-expression of the myogenic differentiation program. The v-myc-transformed myoblasts were phenotypically corrected also by differentiating normal quail myoblasts, giving rise to hybrid myotubes containing nuclei from both cell types. The differential behavior of transformed cells closely paralleled the efficiency with which they established metabolic cooperation with adjacent normal cells. Our results indicate that unrestrained proliferation associated with transformation is responsible for v-myc-induced block of myogenic differentiation.

Animals↗
PubMed1989

A human monoclonal autoantibody isolated from a patient with infectious mononucleosis reactive with both self antigens and Epstein-Barr virus nuclear antigen (EBNA).

In order to investigate the mechanism(s) by which Epstein-Barr virus (EBV) induces the outcome of autoantibodies during infectious mononucleosis (IM), a human IgM (k) monoclonal antibody to cytoskeletal filaments of epithelial cells has been prepared by EBV transformation of peripheral blood B lymphocytes obtained from a patient with IM. The antibody was also found to react with smooth muscle of frozen sections of human stomach tissue by immunofluorescence, and with the Epstein-Barr nuclear antigen (EBNA) by an enzyme-linked immunosorbent assay. These findings demonstrate at the clonal level the epitope homology between host's cell antigens and EBV-encoded nuclear antigen, which might have relevance in EBV-induced autoimmunity.

Antibodies, Monoclonal↗