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Biomedical subjects

M Fazio

Publications and source records attributed to M Fazio.

At least 19 recordsLinked to original sources
PubMed1991

Leukocyte adherence inhibition test: cell-mediated reactivity to tumor antigens in colorectal and lung tumor long survivors.

Cell-mediated immunity versus tumor antigens (cytosols) of the same histotype and site was evaluated by means of the leukocyte adherence inhibition (LAI) test in 44 colorectal adenocarcinoma and 17 lung squamous-cell carcinoma patients 3-10 years after surgical resection. LAI-positivity was observed in 17/44 (38.6%) and 13/17 (76.5%) patients, respectively, together with serum blocking factors in 7/17 (41.2%) compared to 0/13. These results indicate that a high percentage of long survivors retain an immunologic memory of the tumor antigen to which they have been exposed. The prognostic significance of serum blocking factors is less clear.

Adenocarcinoma↗
PubMed1991

Regulation of elastin gene expression.

Recent isolation and characterization of cDNAs encompassing the full length of chicken, cow, and human elastin mRNA have led to the elucidation of the primary structure of the respective tropoelastins. Comparison of the tropoelastin from the different species has revealed that large segments of the sequence are conserved, but considerable variation also exists, ranging in extent from relatively small alterations, such as conservative amino acid substitutions, to large-scale deletions and insertions. Several distinct approaches have yielded compelling evidence of a single elastin gene per haploid genome. Analysis of the bovine and human elastin genes revealed that functionally distinct hydrophobic and cross-link domains of the protein are encoded in separate exons which alternate in the genes. The human gene contains 34 exons, the intron/exon ratio is unusually large (20:1), and the introns contain large amounts of repetitive sequences that may predispose to genetic instability. Comparison of the cDNA and genomic sequences has demonstrated that the primary transcript of both species is subject to considerable alternative splicing, which can account for the presence of multiple tropoelastin isoforms. It is likely that the conformation of elastin is, at least in part, that of a random coil, and therefore it might be expected that the stringency for conservation of the amino acid sequence would be less than that for other proteins with unique conformations. This suggests that functional elastin molecules that vary in their sequence and fitness may exist in the human population and be compatible with a normal life. Potentially though, these variations could have profound consequences on the properties of vital tissues found in the cardiovascular and pulmonary systems over the lifetime of the individual. Consequently, analysis of the structure of the elastin gene and its variation in what is regarded as the normal human population, rather than in those individuals with clearly heritable diseases, assumes greater importance. The 5'-flanking region of the gene is G + C rich and contains several SP-1 and AP2 binding sites, as well as putative glucocorticoid, cAMP, and TPA responsive elements, but no consensus TATA box or functional CAAT box. Primer extension and S1 mapping of the elastin mRNA indicated that transcription was initiated at multiple sites. Transfection experiments using promoter elements/reporter gene constructs demonstrated that the basic promoter element was found within region -128 to -1. In addition, three distinct up-regulatory and two down-regulatory regions were delineated. Taken together, these findings suggest that the regulation of elastin gene expression is complex and takes place at several levels.

Amino Acid Sequence↗
PubMed1991

[Acute effects of transdermal administration of nitroglycerin on effort tolerance and myocardial perfusion, evaluated by Tl-201 scintigraphy, in patients with stable effort angina].

The aim of this study was to evaluate the effects of the transdermal application of nitroglycerin (NGT) on exercise tolerated and regional myocardial perfusion, as evaluated by 201 thallium stress scintigraphy, in patients with stable effort angina. We studied 20 patients, 15 men and 5 women, aged between 43 and 68 years, with average age of 55 +/- 8 years, suffering from effort angina, whose angina threshold was stable in 3 stress testing performed in the week before the study started. The patients, after a pharmacological washout of 1 week, underwent 2 exercise testing 20 hours after the application of a patch containing placebo or 10 mg NGT, with an interval of 7 days. 60-90 s before stress testing was interrupted, 2 mCi of thallium 201 were injected in an antecubital vein of the arm. The scintigraphic images were obtained soon in the 0, 45 and 90 degree views and after 4 hours reperfusion. Under placebo patch all patients interrupted ergometer test for angina, while under the patch containing active NGT angina was present in 11/20 patients and 9 patients stopped the test because of muscular exhaustion. NGT induced an increase of the ergometer test duration (+26%); this difference was statistically significant. The ST segment downsloping decreased significantly both at maximal common work and at exercise peak after NGT application in comparison with placebo. The perfusional defects observed on the scintigraphic images obtained soon after the exercise (and reversible after 4 hours of reperfusion) on placebo patch, diminished significantly after NGT and the captation index lung/heart decreased also significantly (from 49 to 41%), showing so an improvement of cardiac performance. In conclusion the transdermal application of NGT, in patients with effort angina, demonstrated to have antianginal and antiischemic effect, reducing the number of patients interrupting the stress testing for angina, increasing the exercise tolerated and diminishing the ST segment downsloping, objective demonstration of myocardial ischemia. This antianginal and antiischemic effect might follow to the reduction of the preload induced by nitrates, in part also the reduction of the afterload, factors determining a decrease of the wall tension and so of MVO2, but also to a redistribution of the subendocardial flow as demonstrated by 201-Tl scintigraphic images. These effects induce also a global improvement of the left ventricular function as demonstrated by the reduction of the lung/heart index of thallium captation.

Administration, Cutaneous↗
PubMed1990

[Anti-Borrelia burgdorferi antibodies in chronic erythema migrans, benign lymphadenosis cutis, scleroderma and scleroatrophic lichen].

Fiftyone patients with a diagnosis of erythema chronicum migrans (ECM), lymphadenosis cutis benigna (LABC), systemic progressive sclerosis, localized scleroderma and lichen sclerosus et atrophicans were investigated in order to obtain serological evaluation of Borrelia burgdorferi circulating antibodies. In addition sera from 9 patients with pellagroid erythema, prurigo and panniculitis were performed: in these dermatoses there was no evidence of a possible borrelia relationship. Indirect immunofluorescence assay was used for serologic testing. Elevated IgG antibody titers were detected in one female patient with localized scleroderma (1:128) and in one male patient with LABC (1:64). Serologic testing was not positive in the other 58 patients. The very small number of patients with positive antibodies in our study would indicate that Borrelia burgdorferi infection is sporadic in Lazio.

Antibodies, Bacterial↗
PubMed1989

Characterization of the complete human elastin gene. Delineation of unusual features in the 5'-flanking region.

Genomic clones encompassing the entire human elastin gene, including 11 kilobases flanking the ATG translation initiation codon, have been obtained and characterized by restriction enzyme analysis and extensive DNA sequencing. These analyses demonstrated that functionally distinct hydrophobic and cross-linking domains of the protein are segregated into separate exons throughout the gene. All exons are multiples of three nucleotides, and exon:intron borders always split codons in the same way which permits cassette-like alternative splicing. The 5'-flanking region lacks a canonical TATA sequence, is G + C-rich, and contains several SP1 binding sites and an AP2 binding site. Primer extension and S1 nuclease protection experiments indicate that transcription is initiated at multiple sites in the gene.

Amino Acid Sequence↗
PubMed1989

Human nidogen: cDNA cloning, cellular expression, and mapping of the gene to chromosome Iq43.

A human placental lambda gt11 expression cDNA library was screened for nidogen cDNAs by hybridizations with a heterologous mouse nidogen cDNA. A total of four positive overlapping clones were identified, and the sizes of the inserts were shown to vary from 0.8 to 2.8 kb. Nucleotide sequencing of the human cDNAs revealed that the largest clone, cHPN-16, contained both a 5' open reading frame encoding 582 amino acids and a 3' untranslated region of 1,063 nucleotides. Comparison of human cDNA sequences with mouse nidogen sequences revealed 84% identity on the nucleotide level and 88% identity with the deduced amino acid sequence. The deduced amino acid sequence of the human cDNAs revealed the presence of cysteine-rich epidermal growth factor-like repeats and the sequence Arg-Gly-Asp (RGD), a potential cell binding site, two features previously identified in mouse nidogen. The sequence Asn-Pro-Ser, a consensus sequence for N-linked glycosylation, was also noted. The newly isolated human cDNAs were utilized to analyze the expression of the nidogen gene by cultured human cells. Northern hybridizations revealed a single mRNA transcript of approximately 6.0 kb in human skin fibroblast and in HT 1080 fibrosarcoma cell cultures. However, the human choriocarcinoma cell line JEG-3, which expressed laminin genes, did not contain detectable levels of nidogen mRNAs. Quantitation of the relative nidogen mRNA abundance in HT 1080 fibrosarcoma cells indicated that nidogen mRNA levels were approximately the same as those for the laminin B2 chain. Finally, one of the nidogen cDNAs was used to map the nidogen gene onto locus q43 of chromosome 1.

Amino Acid Sequence↗
PubMed1989

Human laminin: cloning and sequence analysis of cDNAs encoding A, B1 and B2 chains, and expression of the corresponding genes in human skin and cultured cells.

A human placental lambdagt11 expression cDNA library was probed for laminin cDNAs by a combination of immunoscreening using polyclonal anti-human laminin antibody, and plaque hybridizations using a mouse laminin A chain cDNA. A total of 36 recombinant clones were isolated and characterized. Northern blot hybridizations with poly(A)+RNA, isolated from cultured human skin fibroblasts, revealed hybridization either to (a) a single 10 kb transcript consistent with A chain; (b) a single 5.7 kb transcript consistent with B1 chain; or (c) polymorphic 5.6 and 8.2 kb transcripts consistent with B2 chain of human laminin. Nucleotide sequencing of representative cDNA clones (approximately 2.5 kb in size) confirmed that these three groups of cDNAs encoded C-terminal sequences of laminin A, B1 and B2 chains, respectively. Deduced amino acid sequences for both B1 and B2 chains contained epidermal growth factor-like sequences and alpha-helical heptad repeats, as found previously for mouse laminin. Partial laminin A chain cDNA encoded 680 amino acid residues characterized by several internal repeats. This portion of the peptide accounted for a large part of the globular domain (fragment 3), the whole length of a second (T2) and portions of a third (T1) globular domain. The human A chain also contained an Arg-Gly-Asp sequence, a potential cell-binding site, which is not found in the same segment of mouse laminin. The newly isolated cDNAs were also utilized to analyze expression of laminin mRNAs by cultured human cells and tissues. The results demonstrated that the laminin A, B1, and B2 chain genes were expressed in an uncoordinate manner in both cultured cells and tissues, with a particularly low level of the A chain mRNA being present.

Amino Acid Sequence↗
PubMed1987

Subungual exostosis. Histological and clinical considerations on 30 cases.

The authors review 30 cases of subungual exostosis, 27 in the foot and 3 in the hand. In approximately 80% of the cases, errors in initial diagnosis had been made, and the affection had been confused with ordinary verrucae, mycoses or pyogenic disease. Histological examination showed that in some cases the neoformation ossified by an enchondral mechanism similar to that of osteocartilaginous exostosis, while more often the mechanism was of the intramembranous or mixed type. The treatment consisted of resection of the exostosis at its base after removing the nail. Complete healing occurred in all cases.

Adolescent↗
PubMed1985

Combined cryosurgical, chemotherapeutic, and radiotherapeutic management of T1-4N0M0 oral cavity cancers.

Eighty-four previously untreated patients (69 males, 15 females) with squamous carcinoma of the tongue (30 patients), floor of the mouth (30), cheek (16), and retromolar region (8) were treated using a protocol comprising cryosurgery + chemotherapy, followed by external 60Co radiotherapy. The follow-up period was at least 6 months (median, 50 months). Cryosurgery (1-2 sessions in 49 T1-2 cases; 2-4 in 35 T3-4 cases) was accompanied by a CMF (cyclophosphamide, methotrexate, 5-fluorouracil) schedule (T1-2, two courses; T3-4, three courses). Radiotherapy was given 15 to 20 days after combined cryochemotherapy (T1, 50 Gy on tumor and lymph nodes; T2-3-4, same with an extra dose of 10 to 15 Gy on the primary lesion). Complete remission was reached 4 months after treatment in 76 of 84 patients (90.5%). Survival with no evidence of disease (NED) in the 57 patients (27 T1-2, 30 T3-4) with a follow-up of more than 3 years was 59.6% for the series as a whole, 70.3% for T1-2, and 50.0% for T3-4; 78.2% for the tongue, 52.6% for the floor, 66.6% for the cheek, and 0% for the retromolar region. The picture was much the same after 5 years. Actuarial survival at 6 years was 66% in the series as a whole, 75.5% in T1-2, and 57.5% in T3-4 (tongue 86.9%, floor 56.1%, cheek 68.4%, and retromolar region 0%). It is believed that the results obtained in tumors of the tongue, floor and cheek, coupled with the conservative aspects of the protocol, make it a suitable subject for a controlled trial.

Adult↗
PubMed1985

Carcinoma of the tongue and floor of the mouth. Preliminary results of a multidisciplinary approach.

UNLABELLED: Eighty-five patients (74 males, 11 females) with untreated squamous-cell carcinoma of the tongue (40 patients) and the floor of the mouth (45 patients) underwent a multidisciplinary treatment. FOLLOW-UP: 6-72 months (median 52 months). T1-4N0M0 lesions (tongue; 32 patients; floor of mouth, 32 patients) were treated with cryosurgery (T1-2: 1-2 sessions, T3-4: 2-4 sessions) and contemporaneously with CMF (cyclophosphamide, methotrexate, fluorouracil) (T1-2: 2 courses; T3-4: 3 courses). 15-20 days after the end of cryo-chemotherapy the patients underwent TCT (T1: 50 Gy to the tumour and lymph nodes; T2-3-4: same with an extra dose of 10-15 Gy to the primary lesion). T1-4N1-3M0 patients (tongue: 8, floor of mouth: 13) received the same cryotherapy and chemotherapy, followed by surgery (13 extended suprahyoid dissections, 8 conservative laterocervical dissections, 1 RND). The actuarial survival rate of patients with tongue tumours after 6 years was 81.4% (N0 87.1%; N+ 60.0%). Four months after treatment, 35 patients had reached complete remission (CR). The probability of remaining in CR for 6 years was 53.6% (N0 56.1%; N+ 50.0%). For tumours of the floor of the mouth the actuarial survival rate was 55.2% (N0 56.5%; N+ 48.6%). Four months after treatment, 38 patients had reached CR. The probability of remaining in CR for 6 years was 59.9% (N0 61.5%; N+ 59.3%). A controlled study is recommended in the light of these results and the conservative nature of the protocol.

Actuarial Analysis↗
PubMed1985

Combined chemotherapy, cryosurgery, and radiotherapy/surgery for oral cancer.

UNLABELLED: One hundred and twelve patients (95 males, 17 females) with untreated squamous-cell carcinoma of the oral cavity underwent a multidisciplinary treatment. FOLLOW-UP: 6-72 months (median 51 months). T1-4N0M0 lesions (tongue, 31 patients; floor, 31 patients; cheek, 17 patients; retromolar, 9 patients) were treated with cryosurgery (T1-2: 1-2 sessions, T3-4: 2-4 sessions) and contemporaneously with (cyclophosphamide, methotrexate, fluorouracil)(CMF) (T1-2:2 courses; T3-4: 3 courses). The patients, 15-20 days after the end of cryo-chemotherapy, underwent TCT (T1: 50 Gy on tumour and lymph nodes; T2-3-4: same with an extra dose of 10-15 Gy on the primary lesion). T1-4N1-3M0 patients (tongue: 8, floor: 13, cheek: 2, retromolar: 1) received the same cryotherapy and chemotherapy, followed by surgery (16 widened suprahyoid dissections, 8 conservative laterocervical dissections, 1 radical neck dissection). Overall actuarial survival at six years was 61.9%: T1-4N0M0 (88 patients) 66.6% (T1-2 76.0%; T3-4 56.9%); T1-4N1-3M0 (24 patients) 44.4% (T1-2 66.6%; T3-4 33.3%). Six-year actuarial survival by site was: tongue (39 patients) 79.2% (N0 85.9%); floor (44 patients) 55.2% (N0 57.1%); cheek (19 patients) 74.2% (N0 68.9%); retromolar (10 patients) 0% (N0 0%). Complete remission was reached four months after treatment by 97 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗