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Biomedical subjects

F Papola

Publications and source records attributed to F Papola.

At least 19 recordsLinked to original sources
PubMed2005

HLA DR/DQ alleles and risk of type I diabetes in childhood: a population-based case-control study.

The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta-parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97-8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77-12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11-0.57; OR=0.07, CI 0.02-0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97-190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36-549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.

Alleles↗
PubMed2005

Characterization of a novel HLA-Cw*02 variant, Cw*0208, in a Caucasian individual.

We describe an additional HLA-Cw*02 variant, HLA-Cw*0208, which has been identified in a renal transplant recipient of Caucasian origin (Italy). After performing preliminary serological typing, we analyzed exons 2 and 3 of the HLA-C locus polymorphism by cloning the amplified DNA and using a sequence-based typing method. The new allele differs from Cw*020202 by one nucleotide substitution at nucleotide 61 (G-->A) of exon 2, which translates to a difference of one amino acid at residue 21 (His-->Arg) of the HLA-C heavy chain. We propose that Cw*0208 was generated by a random point mutation in codon 21 from the Cw*020202 allele, or through gene conversion of Cw*020202 with another allele, probably the Cw*1205 and Cw*1602 alleles.

Alleles↗
PubMed2005

Identification of a novel HLA-A*02 allele, A*027401*.

A novel HLA-A*02 allele was detected in a Caucasian patient from central Italy, requiring a hematopoietic cell transplantation. Direct sequencing identified a variation in one nucleotide position, which was confirmed by cloning. The name A*027401 was officially assigned by the WHO Nomenclature Committee in November 2004. A*027401 differs from A*02010101 by a single G to A substitution at nucleotide position 595 in exon 3. The new variant would lead to a nonsynonymous nucleotide change (GGG to AGG) at codon 175, resulting in a basic Arg in the alpha-helix of the alpha2-domain, in place of a non-polar Gly. The presence of an uncommon variation at a highly conserved nucleotide position could have implications in unrelated hematopoietic cell transplantation.

Alleles↗
PubMed2004

Y chromosomal haplogroup J as a signature of the post-neolithic colonization of Europe.

In order to attain a finer reconstruction of the peopling of southern and central-eastern Europe from the Levant, we determined the frequencies of eight lineages internal to the Y chromosomal haplogroup J, defined by biallelic markers, in 22 population samples obtained with a fine-grained sampling scheme. Our results partially resolve a major multifurcation of lineages within the haplogroup. Analyses of molecular variance show that the area covered by haplogroup J dispersal is characterized by a significant degree of molecular radiation for unique event polymorphisms within the haplogroup, with a higher incidence of the most derived sub-haplogroups on the northern Mediterranean coast, from Turkey westward; here, J diversity is not simply a subset of that present in the area in which this haplogroup first originated. Dating estimates, based on simple tandem repeat loci (STR) diversity within each lineage, confirmed the presence of a major population structuring at the time of spread of haplogroup J in Europe and a punctuation in the peopling of this continent in the post-Neolithic, compatible with the expansion of the Greek world. We also present here, for the first time, a novel method for comparative dating of lineages, free of assumptions of STR mutation rates.

Africa, Northern↗
PubMed2003

Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects.

We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity.

Analysis of Variance↗
PubMed2002

Identification of the novel allele B*4427 and a confirmatory sequence (B*44022).

This report presents a novel allele, HLA-B*4427, which was identified in a bone marrow donor of Caucasian origin, and a confirmatory sequence (B*44022). Sequence analysis revealed the new allele differs from B*44021 by a single nucleotide exchange at position 668 (C-->T), which is located in exon 4. At the protein level, it is the only B*44 variant to produce an Ala in place of a Val at codon 199. Its structure suggests that it may have originated from a point mutation in B*44021 or by gene conversion with a variety of HLA-B alleles. Cloning and sequencing of the allele B*44022 revealed a sequence identical to B*44021 and B*44 exon 4, with the codon GTC (Val) in position 199.

Alleles↗
PubMed2001

A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area.

In this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications in reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny within HG 9 (Rosser et al. 2000), with the deepest branching defined by alleles T (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, with a high rate of male gene flow in the Turkish-Greek area.

Alleles↗
PubMed2000

Sequence analysis of a new HLA-DR11 allele in a Caucasian Italian family: DRB1*11272.

This communication describes a new DRB1*11 allele identified in a familial group of Caucasian individuals from central Italy. The new sequence has been officially named DRB1*11272 by the World Health Organization (WHO) Nomenclature Committee (February 2000). It encodes an HLA antigen serologically recognized as DR11. The sequence variation of this new allele was localized to codon 77 of exon 2. It differs at position 230 from DRB1*11011 allele (A replacing C), and at position 231 from DRB1*1127 (C replacing T). At the amino acid level, the DRB1*11272 mutation is silent with respect to the DRB*1127 phenotype, coding for a synonymous asparagine.

Alleles↗
PubMed2000

[Tissue-typing laboratories for organ transplantation].

The tissue typing laboratory performs genetic analysis: the safety and the reproducibility of results are mandatory, because HLA typing can be crucial both in donor-recipient compatibility assessment for organ transplantation and for the diagnosis of immune related disease. The HLA laboratory should perform analysis, as quickly as possible, in order to define donor-recipient matching and to assess the presence of anti-donor specific antibodies in recipient's serum to prevent iperacute rejection. The aim of this report is to define the guidelines that should be followed in all laboratories for each specific transplantation in order to acquire national and international accreditation, and to obtain the best clinical results.

Histocompatibility Testing↗
PubMed1998

p53 tumor suppressor protein and H-RAS oncogene in maxillofacial tumors: immunohistochemical and genetic investigation, induction chemotherapy response and prognosis evaluation.

The authors carried out immunohistochemical and genetic research on the tumor suppressor protein p53 and H-RAS oncogene in oromaxillofacial neoplasms. The purpose was to verify, genetically, the presence of correlations between the degree of histopathological overexpression (per cent) of oncogenes and chemoresistance. The study was carried out on 15 patients with squamous cell carcinoma of the oromaxillofacial region, of equal histopathological grade (G2), who underwent neoadjuvant chemotherapy: cis-diaminodichloroplatinum (CDDP, 20 mg/m2 i.v. days 1-5) and 5-fluorouracil (5-FU 1000 mg/m2 continuous infusion, volumetric pump 2 ml/h, for 5 days). Restaging was carried out after three cycles of chemotherapy to evaluate clinical response. The p53 immunohistochemical study (clone DO-7) showed a pathological overexpression in 9/15 cases; whereas the genetic exam (PCR method, wild DNA) showed mutations in 5/15 cases, with individual corresponding percentages of 95%, 80%, 70%, 45% and 95%. The H-RAS immunohistochemical study (AB-1) (clone 235-1.7.1) showed a pathological overexpression in 12/15 cases; the genetic exam showed mutations in 9/15 cases, corresponding to, respectively, 90%, 35%, 10%, 20%, 77%, 90%, 85%, 25%, 75%. The response to the neoadjuvant chemotherapy was as follows: 2 partial responses (PR) (90%) in 1 tumor of the cheek and in 1 tumor of the soft palate, with global survival (GS) of, respectively, 18 and 15 months. 1 PR (75%) and 4 PR (55%) in 5 tumors of the gum, with GS of, respectively, 10, 6, 8 , 9 and 8 months. Two objective improvements (OI) in, respectively, 1 tumor of the floor of the mouth and 1 tumor of the gum, with GS of, respectively, 5 and 6 months. Three patients had stable disease (S) in 2 tumors of the tongue and 1 tumor of the gum, with GS of, respectively, 10, 7 and 7 months. Three patients had progression (P) in 2 tumors of the floor of the mouth and in 1 tumor of the cheek, with GS of, respectively, 8, 8 and 6 months. This study showed some correlation between genetic analysis and immunohistochemical investigation of 73.3% of cases for p53 and of 80% of cases for H-RAS (Chi-Square Test: p=0.3089). These data do not permit definition of the range of oncogene overexpression which corresponds to mutation, thus serving as a marker of chemoresistance. However, the cases studied confirm that, in regard to p53, there is a certain degree of correlation between absence of mutations and sensitivity to neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Immunological implications of alterations in the c-Ki-ras and p53 genes in the stepwise progression of colorectal cancer: indications for the improvement of prognosis, biotherapy treatment and tumor biology understanding

Alterations in gene structure and functions involving the c-Ki-ras and p53 genes have been shown to play an important role in the various stages of human colorectal carcinogenesis. However, how these gene alterations cooperate with tumoral mechanisms at an immunological level is not known. To this aim an immunological study of a group of healthy subjects, patients with p53 gene deletions (53D), with c-Ki-ras mutations (KrM) and no gene alterations (53D-KrM-) have made. In a previous study we found that a disregulation between TH1/Th2 cell functions seems to be implicated in the establishment and progression of colorectal cancer disease and that soluble interleukin (IL)-2Receptor (sIL-2R) serum level is involved in this. On this basis we investigated the immunological implications of p53 and c.Ki-ras gene alterations, evaluating the relationhips in the immune network between sIL-2R levels in the serum and immunological parameters (IL-2, IL-4 serum levels; CD3, CD16 and CD19 expression on the surface of peripheral blood mononuclear cells--PBMC). Our results suggest that, in the stepwise progression of colorectal cancer, the c-Ki-ras gene alteration is involved in a switch of the host immune response to a suppressive type which, as we have previously reported, may be a determining or concurrent cause of malignant transformation. Alteration in the p53 gene does not appear to ulteriorly impair the patients' immunological response. Our data supports the role of c-Ki-ras gene mutations and p53 deletions as prognostic markers in the passage of normal tissue to adenoma and adenoma to carcinoma respectively. Moreover, the evaluation of the mechanisms involved in the alterations of c-Ki-ras gene seems to be more important than that of p53 suppressor gene for the improvement of prevention, biotherapy treatment and tumor biology understanding.

Journal Article↗
PubMed1997

[p53 mutation and chemoresistance in oral-maxillofacial squamous cell carcinoma. Role of p53 in the cell cycle control and in the modulating action of chemotherapeutic agents].

p53 is a "tumor suppressor gene" with a basic function in the cellular cycle control and subsequently in the induction of the neoplastic process. p53 found changed in the majority of malignant human tumors. In the oral and maxillofacial cancers p53 mutations varies from 4% to 60% of the cases. Researches in vitro in tumors of the colon-rectum, breast, lung, ovary, testicle, bladder and in leukaemia, show a correlation between p53 overexpression (mutation) and resistance to the anti-tumor agents. The functional connection between the p53 and the chemotherapic drugs action which cause a direct DNA damage, is the apoptosis, a physiologic mechanism activated by p53 for regulating cell growth but also indispensable for the cytotoxic effects (apoptosis is an irreversible process culminating in cell death). Loss of the p53 activity (mutation) in the tumoral cells determines non-activation of the apoptosis and the drug resistance. These results have led to early clinical applications. In the breast cancers the p53 is already utilized as chemoresistance marker, directing the therapy, if changed to alternative drugs (Taxolo) which have a p53-independent action. Even into cell lung cancers a retroviral vector containing the wild-type p53 gene was produced to mediate transfer of wild-type p53, noting tumor regression. In oral and maxillofacial tumors surgery is elective. It is emphasized that, in advanced cancers, it is included in multimode protocols where the neoadjuvant chemotherapy has an important clinical function, with precise indications. The possibility to determine previously the p53 "status" in the cancer cells by genetic study, may give a specific factor of screening, indicative of the tumor chemoresponse, together with other well-known prognostic factors, with advantage for the therapeutic programming and especially for the known surgical treatment.

Antineoplastic Combined Chemotherapy Protocols↗