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G Carrieri

Publications and source records attributed to G Carrieri.

At least 19 recordsLinked to original sources
PubMed2001

Mitochondrial DNA haplogroups and APOE4 allele are non-independent variables in sporadic Alzheimer's disease.

Allele epsilon4 of the nuclear APOE gene is a leading genetic risk factor for sporadic Alzheimer's disease (AD). Moreover, an allele-specific effect of APOE isoforms on neuronal cell oxidative death is known. Because of the role of the mitochondrial genome (mtDNA) in oxidative phosphorylation and oxidative stress, an interaction between APOE polymorphism and mtDNA inherited variability in the genetic susceptibility to sporadic AD can be hypothesized. We have explored this hypothesis by analyzing mtDNA germline variants (mtDNA haplogroups) in a sample of AD patients (213 subjects) genotyped for APOE and classified as APOE epsilon4 carriers and non-carriers. We found that the frequency distribution of mtDNA haplogroups is different between epsilon4 carriers and non-carriers (P=0.018), thus showing non-random association between APOE and mtDNA polymorphisms. The same analysis, carried out in two samples of healthy subjects (179 age-matched and 210 individuals aged more than 100 years), showed independence between epsilon4 allele and mtDNA haplogroups. Therefore, the APOE/mtDNA interaction is restricted to AD and may affect susceptibility to the disease. In particular, some mtDNA haplogroups (K and U) seem to neutralize the harmful effect of the APOE epsilon4 allele, lowering the epsilon4 odds ratio from statistically significant to non-significant values.

Aged↗
PubMed2001

Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians.

Previous studies have shown that mitochondrial DNA (mtDNA) haplogroup J is significantly over-represented in healthy centenarians with respect to younger controls, thus suggesting that this haplogroup predisposes to successful aging and longevity. On the other hand, the same haplogroup is reported to have elevated frequency in some complex diseases. To verify if centenarians clustered in a particular lineage within J we have sequenced the D-loop region from 18 centenarians and 18 younger controls, previously characterized to be J. Then the entire mtDNA molecule was sequenced in a sub-sample of nine centenarians to find possible functional mutations associated with haplogroup J in successful aging. No clustering of the J haplogroup mtDNA from centenarians was observed. In addition, most of the mutations found are known as disease-associated mutations. The general picture that emerges from the study is that the J haplogroup of centenarians is surprisingly similar to that found in complex diseases, as well as in Leber Hereditary Optic Neuropathy. This finding implies that the same mutations could predispose to disease or longevity, probably according to individual-specific genetic backgrounds and stochastic events. This data reveals another paradox of centenarians and confirms the complexity of the longevity trait.

Aged↗
PubMed2000

Does a retrograde response in human aging and longevity exist?

The retrograde response (RR) is a compensatory mechanism by which mutant strains of yeast are able to cope with mitochondrial DNA (mtDNA) impairments by up-regulating the expression of the stress-responder nuclear genes and significantly increasing lifespan. Starting from the observation that both mtDNA variability and Tyrosine hydroxylase (THO, stress-responder gene) variability are correlated with human longevity, we asked ourselves whether mechanisms similar to RR may exist in humans. As a first investigative step we have analyzed the distribution of the mtDNA inherited variants (haplogroups) according to THO genotypes in three sample groups of increasing ages (20-49 years; 50-80 years; centenarians). We found that the mtDNA haplogroups and the THO genotypes are associated randomly in the first group, while in the second group, and particularly in the centenarians, a non-random association is observed between the mtDNA and nuclear DNA variability. Moreover, in centenarians the U haplogroup is over-represented (p=0.012) in subjects carrying the THO genotype unfavorable to longevity. On the whole these findings are in line with the hypothesis that longevity requires particular interactions between mtDNA and nuclear DNA and do not exclude the possibility that an RR has been maintained throughout evolution and it is present in higher organisms.

Adult↗
PubMed2000

Inherited variability of the mitochondrial genome and successful aging in humans.

Increasing data indicate that polymorphic variants of nuclear loci can affect rate and quality of aging in humans. However, the mitochondrial genome is another good candidate, because of the central role played by mitochondrial genes in oxidative phosphorylation (OXPHOS) and cell metabolism. A characteristic of the mitochondrial genome (mtDNA) is the high level of interindividual variability that ensues from high mutation rate and unilinear inheritance. Related groups of germline/inherited mtDNA polymorphisms (haplogroups) have been identified as continent-specific sets of stable/ancient/associated restriction fragment length polymorphisms in the mtDNA coding region, representing markers capable of exactly depicting the mtDNA pool of a specific population. The hypothesis can be put forward that mtDNA variants included in a haplogroup may have similar OXPHOS efficiency and therefore act as genetic factors predisposing to individual successful or unsuccessful aging. This idea can be explored by sampling groups of individuals of different ages from a well-defined population and comparing the pools of mtDNA haplogroups between samples. The results obtained by screening mtDNA haplogroups in about 800 Italians of different ages, including more than 200 centenarians, agree with the hypothesis that the inherited variability of the mitochondrial genome is associated with the chance of successful aging and longevity in humans.

Aging↗
PubMed1999

Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans.

Mitochondrial DNA (mtDNA) is characterized by high variability, maternal inheritance, and absence of recombination. Studies of human populations have revealed ancestral associated polymorphisms whose combination defines groups of mtDNA types (haplogroups) that are currently used to reconstruct human evolution lineages. We used such inherited mtDNA markers to compare mtDNA population pools between a sample of individuals selected for successful aging and longevity (212 subjects older than 100 years and in good clinical condition) and a sample of 275 younger individuals (median age 38 years) carefully matched as to sex and geographic origin (northern and southern Italy). All nine haplogroups that are typical of Europeans were found in both samples, but male centenarians emerged in northern Italy as a particular sample: 1) mtDNA haplogroup frequency distribution was different between centenarians and younger individuals (P=0.017 by permutation tests); and 2) the frequency of the J haplogroup was notably higher in centenarians than in younger individuals (P=0.0052 by Fisher exact test). Since haplogroups are defined on the basis of inherited variants, these data show that mtDNA inherited variability could play a role in successful aging and longevity.

Adult↗
PubMed1998

Age-related changes of the 3'APOB-VNTR genotype pool in ageing cohorts.

The analysis of seven different age cohorts (697 individuals from 10 to 109 years old) revealed age-related changes in the 3'APOB-VNTR genotype pool. By recoding the 3'APOB-VNTR alleles into three size-classes (small, S, 26-34 repeats; medium, M, 35-39 repeats; large, L, 41-55 repeats), an age-related convex trajectory of the frequency of SS homozygotes was found. The frequency of SS in the genotype pool increased from the group aged 10-19 years (3.06 +/- 1.74%) to that aged 40-49 years (8.51 +/- 4.07%). Then it declined reaching the minimum value in centenarians (1.58 +/- 0.90%). The observed trajectory is in agreement with that expected by assuming crossing of mortality curves relevant to subgroups of individuals having different genotypes.

Adolescent↗
PubMed1996

Allele frequency distributions at seven DNA hypervariable loci in a population sample from Calabria (southern Italy).

Genotype and allele frequencies at seven Variable Number of Tandem Repeats (VNTR) loci currently used for forensic purposes have been estimated in a population sample from Calabria (south Italy). DNA target regions relevant to four microsatellites (THO.1; REN.4; D12S67; DYS19) and three minisatellites (D1S80; 3'APOB; TPO.10) were amplified by Polymerase Chain Reaction (PCR) and analysed by electrophoresis and ethidium bromide or silver staining. For all loci, the observed genotypes were found to be in agreement with those expected by the Hardy-Weinberg equilibrium. Data on allele frequencies were in line with those found in sample groups from northern or central Italy, tested for some of the above polymorphisms.

Adolescent↗
PubMed1996

[Echo-guided percutaneous treatment of renal cysts: aspiration vs continuous 24-hour drainage].

The results of 2 treatment options, percutaneous aspiration vs percutaneous aspiration and continuous drainage over 24 hours, in the management of simple renal cyst were compared. Thirteen patients were managed with aspiration alone (group 1) while 19 with aspiration and continuous drainage (group 2). Recurrence rate was 100% in group 1 and 73% in group 2 (p: n.s.). Therefore, we believe that the higher cost of continuous drainage are not justified.

Adult↗
PubMed1996

[Renal peripelvic multicystic lymphangiectasia: is echographic diagnosis possible?].

We describe the role of US, in the diagnosis of LMPR and in differentiating LMPR from other renal disease, such as hydronephrosis and parapelvic cysts. In 10 patients mild to moderate hydronephrosis showed at the US, bilateral in 8 cases, was not confirmed at IVP and CT scan evaluation. Instead, compression of the collecting system by multiple cysts arising from the renal sinus was revealed by CT scan in 8 cases and by IVP in 2. At the U.S. the profile of the calices appeared irregular, differing from the features of hydronephrosis; furthermore calices were adjacent each other, separated only by a thin membrane. All patients were asymptomatic. The examination of the cystic liquor and wall, obtained percutaneously or during surgical procedures, showed the lymphatic origin of them. We cannot provide definitive data regarding how to differentiate LMPR from hydronephrosis at U.S.. In asymptomatic patients the U.S. evidence of dilated calices with irregular profile and thin membrane separating each other, can strongly suggest the diagnosis of LMPR.

Diagnosis, Differential↗
PubMed1996

[Role of color Doppler echography (ECD) in the diagnosis and follow-up of post-biopsy arteriovenous fistula in the transplanted kidney].

CCD is an helpful imaging technique during biopsy of transplanted kidney, since it has reduced the incidence rate of complications associated to this procedure. Among possible complications one of the most frequent is the arteriovenous fistula. We report our experience with CCD in diagnosis and monitoring of this complication and we underline its role in case of conservative management.

Arteriovenous Fistula↗
PubMed1994

FK506 "rescue" for resistant rejection of renal allografts under primary cyclosporine immunosuppression.

Seventy-seven patients with ongoing acute rejection on initial CsA therapy were converted to FK506 to attempt graft salvage. Fifty-nine patients had undergone primary transplantation and 18 had been retransplanted; there were 52 cadaveric and 25 living-donor transplants. The indications for conversion to FK506 were ongoing, biopsy-confirmed rejection in all patients, including vascular rejection in 20. The median interval to rescue was 2 months (range 2 weeks to 36 months) after transplantation. Sixty-one of the 77 patients (79%) had already received one or more courses of an antilymphocyte preparation (OKT3: n = 33; ALG or ATG: n = 1; OKT3+ALG/ATG: n = 27). Of the 77 patients, 57 (74%) have been successfully rescued and still have functioning grafts with a mean follow-up of 14 months, with a mean serum creatinine of 2.35 +/- 0.97 mg/dl. Eighteen patients were already dialysis-dependent at the time of conversion to FK506; of these, 9 (50%) were successfully salvaged and have a mean serum creatinine of 2.3 mg/dl. Of the 61 patients previously treated with antilymphocyte preparations, 48 (79%) were rescued. In those salvaged, prednisone doses have been lowered from 22.2 +/- 7.2 mg/day preconversion to 7.5 +/- 5.6 mg/day postconversion, and 12 patients are on FK506 monotherapy. In nondiabetics, mean serum glucose was 101.4 +/- 20.5 mg/dl preconversion and 93.2 +/- 22 postconversion (P = 0.07), uric acid 7.3 +/- 2.3 and 7.1 +/- 1.5 mg/dl (P = 0.53), and triglycerides 199.2 +/- 101.6 and 167.2 +/- 106.4 mg/dl (P = 0.06). Cholesterol levels were significantly lower following FK conversion (207.7 +/- 46.5 mg/dl pre. vs. 188.3 +/- 39.7 post., P = 0.007). FK506 is capable of salvaging renal allografts with ongoing acute rejection on CsA therapy, even when antilymphocyte preparations have been ineffective.

Adolescent↗
PubMed1994

Dermatological toxicity from chemotherapy containing 5-fluorouracil.

5-Fluorouracil (5-FU) is an antimetabolite frequently used in the treatment of cancer. The most common adverse reactions are acute gastrointestinal effects and bone marrow suppression while neurological, ocular and dermatological toxicities are unusual. Several cutaneous manifestations can be found. They are hyperpigmentation, maculo-papular eruption and palmar-plantar erythrodysesthesia (PPES) promptly reversed with discontinuation of 5-FU. The etiopathogenesis of such manifestations is still unknown particularly as regards PPES, but it has been postulated that the local drug accumulation secondary to different scheduling (continuous infusion instead of bolus infusion), the total amount of drug, alcoholism, local trauma, increased blood flow could be responsible for them. In this study we have reported 10 cases of dermatological toxicity (1 of these had PPES) observed from January '91 to December '93 in 81 patients treated with bolus injection of 5-FU containing combination chemotherapy.

Adult↗
PubMed1994

[Diltiazem helps perfusion of the kidney after transplantation: intraoperative assessment using echo-color Doppler].

Diltiazem is a dihydropyridinic calcium-antagonist which acts an arterial muscle, producing an increase in vascular capacity. We administered it intraoperatively in 2 patients subjected to kidney transplantation, to asses the maximal vascular reserve of the transplanted organ. After 2' and 10' from administration of Diltiazem, Color Doppler Ultrasound showed a 30% increase in mean flow in the renal artery and 13% reduction in the intraparenchymal resistance rates with respect to the basal parameters. Systemic arterious pressure remained unchanged. This result was associated with an improvement in the perfusion of the transplanted organ.

Diltiazem↗
PubMed1994

[Transrectal echography of the prostate in the long-term follow-up of prostatic carcinoma in advanced stage].

In the last eight years, 60 patients with carcinoma of the prostate in an advanced stage underwent transrectal ultrasound examinations of the prostate both before and after treatment with LHRH analogues, alone or associated with antiandrogens. Mean follow-up was 30 months (9-96 months) and mean survival 33 months (9-81). In all patients, the volume and echogeneicity of the prostate were assessed before treatment and once every three months thereafter. A significant reduction in volume was observed in 91% of the cases (54/60), while a variation in the echogeneicity was noted in 80% of the patients (48/60); these data do not seem to have been affected by the type of treatment administered. The greatest reduction in volume occurred during the first three months, after which a virtually constant volume was observed. Metastatic progression occurred in 29 of the 60 patients assessed, whereas no increase in prostate volume was demonstrated by ultrasound in 18 of these patients. These data, reported by other authors, too, may indicate that transrectal ultrasound examinations alone cannot constitute a complete follow-up in prostatic carcinoma: they can only show local progression and should therefore be associated with other diagnostic methods, in particular the specific prostate antigen.

Follow-Up Studies↗
PubMed1994

[Echo-color Doppler in renal transplantation: the clinician's needs].

Kidney transplantation can lead to a number of complications of a urological and/or vascular nature. Early diagnosis of these complications may determine the survival of the organ. While diagnosis of urological-type complications can be made by means of non-invasive techniques like ultrasound investigation, vascular-type complications often require invasive techniques using contrast medium, such as angiography. Recently, the possibility of using color doppler ultrasound, both intraoperatively and for follow-up, has been suggested, as a means not only of assessing anastomosis and renal perfusion but also of diagnosing any complications of a vascular nature. In the last two years, 51 kidney transplants have been performed at our centre; all patients underwent color doppler ultrasound. We report our experience paying particular attention to vascular complications.

Humans↗
PubMed1993

Suppression of autoimmune thyroid disease by FK 506: influence on thyroid-infiltrating cells, adhesion molecule expression and anti-thyroglobulin antibody production.

Autoimmune thyroid disease was induced in female PVG/c rats by neonatal thymectomy, followed by sublethal, whole body x-irradiation. Disease development, assessed by histological evidence of lymphocytic thyroiditis and circulating levels of anti-thyroglobulin antibodies, was reduced significantly by a 3-week course of FK 506 (0.5 or 1.5 mg/kg per day) commencing after the detection of autoantibody production. Thyroid-infiltrating mononuclear cells (MNC) in untreated rats stained predominantly for CD4+ and MHC class II antigen which was expressed widely on dendritic cells. Fewer infiltrating cells expressed TCR alpha/beta, CD5, CD8 or LFA-1 beta. Intercellular adhesion molecule-1 (ICAM-1) was observed on MNC, vascular endothelial cells and a minority of residual thyroid epithelial cells. FK 506 administration reduced markedly the incidence of infiltrating TCR alpha/beta +, CD5+, CD4+, CD8+, and LFA-1 beta + cells and the expression both of MHC class II antigens and ICAM-1 on MNC, endothelial cells and thyrocytes. Compared with normal PVG/c rats, there were reduced incidences of CD4+ CD8- and CD4- CD8+ lymphocytes and an elevation in the CD4+/CD8+ cell ratio in the spleens of animals with autoimmune thyroiditis. These changes were partially reversed by FK 506. Systemic drug levels estimated by enzyme immunosorbent assay were in excess of those known to blockade cytokine production by CD4+ T lymphocytes in vitro and some evidence of minor renal dysfunction was observed. The results are consistent with a therapeutic effect of FK 506 mediated via interference with CD4+ T lymphocyte function and adhesion molecule-dependent cytotoxic effector mechanisms.

Animals↗