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P Rizzo

Publications and source records attributed to P Rizzo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evidence for and implications of SV40-like sequences in human mesotheliomas and osteosarcomas.

Pleural mesotheliomas and osteosarcomas develop in hamsters injected intracardially with SV40. Using primers specific for the RB-pocket binding domain of SV40 we analysed with the polymerase chain reaction frozen specimens from 48 human mesotheliomas and 145 human bone tumours. We found that 60% of human mesotheliomas and 33% of human bone tumours contained SV40-like DNA. Immunostaining, Western blot and RNA in situ hybridization experiments revealed SV40 Tag expression in human mesotheliomas. Osteosarcomas were not studied for Tag expression because not enough material was available. Finally, antibodies anti-Tag were detected in the sera collected from patients with mesothelioma. These data indicate that SV40, or a closely related virus, is/are present in human mesothelioma and osteosarcoma.

Animals↗
PubMed1998

Further validation of SV40-like DNA in human pleural mesotheliomas.

We have confirmed in a second set of patients having human pleural mesothelioma that DNA for regions of the amino terminus of SV40 Tag can be amplified by the polymerase chain reaction. Moreover, other regions, including the carboxy terminus for Tag, and the regulatory region of SV40, are present in these specimens.

DNA, Viral↗
PubMed1998

Simian virus 40 oncogenesis in hamsters.

Simian virus 40 (SV40) is a DNA tumour virus which is highly oncogenic in hamsters. Only specific histologic types of tumours develop in hamsters injected with SV40, and these are influenced by the route of virus inoculation. When SV40 is injected systemically to expose most different cell types to the virus, the animals develop mesotheliomas, osteosarcomas, sarcomas, and lymphomas within six months. When the virus is injected subcutaneously, sarcomas at the site of injection develop. If hamsters are injected intracranially with SV40, they develop ependymomas. These same tumour types have been found to contain SV40.

Animals↗
PubMed1997

Simian virus 40, poliovaccines and human tumors: a review of recent developments.

Recently, wild-type SV40 and/or DNA sequences indistinguishable from SV40 have been detected in specific types of human tumors: ependymoma and choroid plexus tumors, mesothelioma, osteosarcoma and sarcoma. The same tumor types will develop in hamsters after injection with SV40. These findings are interesting in themselves for they could shed light on the pathogenesis of these tumors. These findings also have public health implications. SV40 was found to have contaminated the poliovaccines and the adenovaccines from 1955 until 1963, therefore resulting in the inadvertent injection of millions of people with this tumor virus. Moreover, our society pays a high cost for asbestos causality, a carcinogen associated with the development of mesothelioma. In addition to asbestos, the potential impact of finding another possible cause for mesothelioma (i.e., SV40), as well as the possible pathogenic role of the contaminated poliovaccines, has generated considerable public interest and concern. To discuss these recent findings, the NIH (National Institutes of Health) and the FDA (Food and Drug Administration), organized an International Conference at the NIH, Bethesda, MD, January 27-28, 1997. The association of SV40 with human mesothelioma was also discussed in a special session at the IV International Mesothelioma Conference that was held at the University of Pennsylvania, Philadelphia, PA, May 13-16, 1997. The purpose of this review is to summarize data, from the discovery of the contaminated poliovaccines, to the most recent findings presented at the meetings in Bethesda and Philadelphia, to discuss technical and other problems associated with this research, and the potential for using these findings to develop new diagnostic and therapeutic approaches for SV40-associated malignancies.

Animals↗
PubMed1997

Simian virus-40 large-T antigen binds p53 in human mesotheliomas.

We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that 60% of human mesotheliomas contain and express SV40 sequences, results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus," NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated.

Antigens, Polyomavirus Transforming↗
PubMed1997

The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas.

The oncoprotein of simian virus-40, SV40 large T-antigen (Tag), is reported to target and to inactivate growth suppressive proteins such as the retinoblastoma family and p53 (ref. 4, 5), leading to transformation of human cell lines in vitro, tumor production in rodents, and detection of Tag in several human cancers including mesotheliomas. The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner, have cell growth suppressive properties and bind to specific members of the E2F family and various cyclins. Even though mesotheliomas are among the most aggressive human cancers, alterations of important cell-cycle "controllers," such as the Rb family genes, have never been reported in these tumors. We found the presence of SV40-like sequences in 86% of 35 archival specimens of mesothelioma. We also demonstrated that SV40 Tag, isolated from frozen biopsies of human mesothelioma, binds each of the retinoblastoma family proteins, pRb, p107 and pRb2/p130, in four of four specimens. We propose that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumor and/or growth suppressive proteins.

Adult↗
PubMed1996

SV40-like sequences in human bone tumors.

Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas when injected in hamsters. Recently, approximately 60% of human ependymomas, choroid plexus tumors and mesotheliomas were reported to contain and express SV40-like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene, 1994, 9, 1781-1790). In this study the presence of SV40-like sequences was investigated in additional types of human tumors. Initially, 200 tumor and normal tissue DNA samples were analysed by polymerase chain reaction (PCR) with primers that amplify a 574 base pair region of SV40 large T antigen (Tag), which includes the Rb-pocket binding domain and the intron of Tag. PCR amplification and Southern blot hybridization with a probe specific for SV40 Tag revealed that 18/200 samples contained SV40-like sequences and, unexpectedly, 11/18 were from patients with osteosarcomas. Additional DNA samples from bone tumors were then analysed. In 40/126 osteosarcomas, and 14/34 other bone-related tumors, Tag sequences could be amplified. Sequence analysis of the DNA amplified from seven different tumors confirmed that the amplified sequences corresponded to SV40 Tag, with some demonstrating deletions in the intron region but not in the Rb-pocket binding domain. The extent of SV40 genome sequences present in the DNA samples was further analysed in two osteosarcomas. PCR amplification, Southern blot hybridization, and sequence analysis revealed that these samples also contained sequences for the carboxy-terminal domain of Tag, the viral regulatory region, and the VP1 capsid protein. These results indicate that SV40-like sequences are present in human bone tumors.

Base Sequence↗
PubMed1996

Oncogene alterations in primary, recurrent, and metastatic human bone tumors.

We investigated the structure and the expression of various oncogenes in three of the most common human bone tumors-osteosarcoma (36 samples from 34 patients), giant cell tumor (10 patients), and chondrosarcoma (18 patients)-in an attempt to identify the genetic alterations associated with these malignancies. Alterations of RB and p53 were detected only in osteosarcomas. Alterations of c-myc, N-myc, and c-fos were detected in osteosarcomas and giant cell tumors. Ras alterations (H-ras, Ki-ras, N-ras) were rare. Chondrosarcomas did not contain any detectable genetic alterations. Our results suggest that alterations of c-myc, N-myc, and c-fos oncogenes occur in osteosarcomas, in addition to those previously described for the tumor suppressor genes RB and p53. Moreover, statistical analyses indicate that c-fos alterations occur more frequently in osteosarcoma patients with recurrent or metastatic disease.

Adolescent↗
PubMed1996

Scattering of 60 keV photons by biological material and influence in diagnostic radiology.

The angular and energy distributions of photons scattered by water, muscle tissue, and bone were measured at the Physics Institute of the Universidade Federal do Rio de Janeiro using a Ge-detector and a 241Am source of 59.54 keV radiation. Single and double scattering were investigated on samples up to 16 cm in diameter. The results were compared with theoretical calculations of Rayleigh (elastic) and Compton (inelastic) scattering, assuming a simple model for the scattering geometry. The overall agreement between model and experimental results for soft tissue and water allows quantitative predictions based on a simple equation. Some applications are presented.

Biophysical Phenomena↗
PubMed1994

Simian virus 40-like DNA sequences in human pleural mesothelioma.

Mesotheliomas are pleural, pericardial, or peritoneal neoplasms frequently associated with asbestos exposure, and it is estimated that over the next twenty years up to 80,000 new cases are expected in the USA alone. We found simian virus 40-like DNA sequences in 29 of 48 mesotheliomas studied (60%) and demonstrated simian virus large-T antigen expression in 13 of 16 specimens. The matching lung samples did not contain simian virus 40-like sequences; however, they contained asbestos. These findings are to our knowledge the first demonstration of a physical link between DNA virus-like sequences and human mesothelioma. We suggest that a simian virus 40-like virus may act independently or as a co-carcinogen with asbestos. Moreover, the selective large T antigen expression by mesothelioma and not by the surrounding pulmonary parenchyma may have both diagnostic and therapeutic implications.

Adult↗
PubMed1992

A study of hydrogen exchange of monoclonal antibodies: specificity of the antigen-binding induced conformational stabilization.

Amide-hydrogen exchange of three anti-yeast iso-1-cytochrome-c IgG monoclonal antibodies and the Fab, prepared from one of them, were studied by infrared spectrophotometry in the presence and absence of the deuterated immunogen and evolutionarily related species (the deuterated immunogen contained a population of a dimer. Each subunit of the dimer appeared to bind to the antibodies in a manner similar to the monomer). The number of hydrogens of the antibodies whose exchange was suppressed on binding to the immunogen was found to exceed that estimated for the residues shielded by the immunogen. Analysis of the data suggests that such suppression of hydrogen exchange occurs mainly for the Fab domains, but not for the Fc. One of the antibodies showed two distinct classes of amide-hydrogens. Class-1 hydrogens (approx. 36/site) exchange faster than class 2 (approx. 37/site). The exchange of class-1 hydrogens was suppressed by binding to the immunogen, but not to the evolutionarily related species. The exchange of class-2 hydrogens was suppressed by binding to the evolutionarily related species, as well as to the immunogen. Thus, the suppression of exchange of class-1 hydrogens appears to occur by some kind of conformational stabilization, the mechanism of which differentiates between the deuterated immunogen and the evolutionarily related species. Evidence suggests that the trans-interactions of the Fab domains may modulate the hydrogen exchange. If it is assumed that the antigen-binding strengthens the trans-interactions in such a way that the exchange of the slower exchanging hydrogens is suppressed, this could explain the suppression of exchange of class-2 hydrogens.

Amides↗
PubMed1991

Simultaneous recording of pattern electroretinogram (PERG) and visual evoked potential (VEP) in multiple sclerosis.

We studied 18 multiple sclerosis (MS) patients affected by retrobulbar neuritis (RBN). The patients were subdivided into two groups. Group 1: 14 patients with RBN. Group 2: 4 patients with optic atrophy. An ophthalmological examination (visual acuity, fundus oculi, visual field) was carried out in all the patients. A simultaneous visual evoked potential (VEP) and pattern electroretinogram (PERG) recording at two spatial frequencies (45' and 15') was performed. All the data obtained in Group 1 were compared (Student T-Test) with those of a control group of normal subjects matched for age and sex. Group 1. VEP: a comparison of the data in MS patients affected by RBN with the control group revealed a statistically significant P100 latency delay with both spatial frequencies (P less than 0.001). PERG: no "b" wave latency change at 45' and 15' spatial frequencies were seen. A "b" wave amplitude reduction was observed; this reduction reached significant values at 45' (P less than 0.001). Group 2. In optic atrophies the PERG was absent in 4 eyes at 45' and in 5 eyes at 15'.

Adult↗
PubMed1989

Short-latency sinusoidal wavelets to bright flashed stimuli: studies with corneal lens, nasopharyngeal, retrobulbar and scalp recordings.

Short-latency flash visual evoked potentials (VEPs) and electroretinograms (ERGs) were recorded in 30 healthy volunteers and 14 patients (7 with retrobulbar neuritis and 7 with retinitis pigmentosa). Simultaneous recordings were performed by corneal, scalp, nasopharyngeal and retrobulbar (5 patients) electrodes. In 18 out of 30 healthy controls a brief sequence of oscillating wavelets was recorded between 15 and 40 ms on the scalp sites behind the vertex. In retrobulbar neuritis (RBN) patients normal responses were recorded by lens, retrobulbar, nasopharyngeal and frontal scalp electrodes. On the contrary none of these patients displayed short-latency activity behind the Cz scalp position. In 5 out of the 7 patients with retinitis pigmentosa, corneal, nasopharyngeal and scalp electrodes failed to detect any reliable waveform time-locked to the flash onset. In the remaining 2, a small lens ERG was recorded, while all other electrodes recorded a sequence of low-volted wavelets initiating 30 ms after the stimulus onset. In these patients an occipital VEP reduced in amplitude and with prolonged latency was also recorded. It is concluded that in presence of a normal corneal ERG because of the presence of volume spread oscillating retinal activity, it is hard to define while part of the scalp recorded, short latency, oscillating potentials is generated in subcortical visual structures.

Adolescent↗
PubMed1989

Axillary dissection for breast carcinoma. The myth of skip metastasis.

The question of what constitutes an adequate axillary dissection for breast cancer remains open for debate. Central to this controversy is whether axillary nodal metastasis occurs in a stepwise fashion or spreads sporadically, creating skip metastases. The therapeutic aim of axillary dissection also must be considered. To resolve this controversy, a prospective study involving 129 patients who underwent complete axillary dissection for breast carcinoma was performed. The tissue from the axillary dissections was divided intraoperatively and sent to the pathologist as two specimens. The first specimen contained all nodes lateral to the pectoralis minor muscle (Level I), whereas the second contained all nodes beneath and medial to the pectoralis minor (Levels II and III). The tissue was analyzed to determine the frequency of skip metastasis. Only two patients, 1.6 per cent of the total group or 3.2 per cent of the positive node group, were found to have a positive node in Level II-III with no metastasis in Level I. A thorough dissection of Level I alone is sufficient to detect more than 98 per cent of all axillary lymph node metastases from breast cancer. Thus, proper staging of the disease can be obtained. When Level I contained positive nodes, the probability of metastatic disease to higher levels was significant (45%), indicating further treatment is necessary in incomplete axillary dissections.

Breast Neoplasms↗
PubMed1986

Interneural and intervascular extension for increased exposure in midline vertical incisions.

In instances in which wide upper lateral abdominal exposure is required, standard midline incisions are occasionally inadequate. The typical invered "U" incision violates the nerve and blood supply to the abdominal wall. An interneural and intervascular incision which is used either as an extension of the midline incision or bilaterally as the primary incision is described herein. The interneural and intervascular extension begins at the costal margin and curves medially with severance of the full thickness abdominal wall to join the vertical midline incision. This extension raises a triangular flap of abdominal wall with a base on the costal cartilage and apex at the junction of the two incisions. In a series of seven patients, no interneural and intervascular incision resulted in wound hernia or delayed wound healing postoperatively. This approach provides superior lateral abdominal exposure and by paralleling nerve and vascular distribution, follows sound anatomic principles for minimizing pain and promoting subsequent wound healing.

Abdominal Muscles↗