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M Marchini

Publications and source records attributed to M Marchini.

At least 19 recordsLinked to original sources
PubMed2007

Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe.

We obtained eight collections of DNA samples from ethnically matched systemic lupus erythematosus (SLE) patients and controls from five European countries totaling 783 patients and 1210 controls. A highly significant cline in the frequency of the PD1.3 A allele was found among controls but not among SLE patients. The frequency of the PD1.3 A allele increased from the Northeast to the Southwest of Europe. The cline was clearly apparent (P=1.2 x 10(-6)) when data from controls of other five SLE susceptibility studies were included in the analysis. This variation has severely biased SLE association studies owing to the lack of parallel changes in SLE patients. As a consequence, the PD1.3 A allele was more common in SLE patients than in controls in the Northeast and Center of Europe, similar to controls in Southeast Europe, and less frequent than in the controls in the Southwest of the Continent. This dissociation in allele frequencies between SLE patients and controls in different subpopulations indicated that programmed cell death 1 variation and disease susceptibility are not independent but the type of relationship is currently unclear. As allele frequency clines are common in other polymorphisms their impact in genetic epidemiology studies should be carefully considered.

Antigens, CD↗
PubMed2007

Ultrastructural characterization of calcification onset and progression in subdermally implanted aortic valves. Histochemical and spectrometric data.

Detailed characterization of the subdermal model is a significant tool for better understanding of calcification mechanisms occurring in heart valves. In previous ultrastructural investigation on six-week-implantated aortic valve leaflets, modified pre-embedding glutaraldehyde-cuprolinic-blue reactions (GA-CB) enabled sample decalcification with concurrent retention/staining of lipid-containing polyanionic material, which lined cells and cell-derived matrix-vesicle-like bodies (phthalocyanin-positive layers: PPLs) co-localizing with the earliest apatite nucleation sites. Additional post-embedding silver staining (GA-CB-S) revealed PPLs to contain calcium-binding sites. This investigation concerns valve leaflets subjected to shorter implantation times to shed light on the modifications associated with PPLs generation and calcification onset/progression. Spectrometric estimations revealed time-dependent calcium increase, for unreacted samples, and copper modifications indicating an increase in acidic, non-glycanic material, for GA-CB-reacted samples. Two-day-implant thin sections showed emission and subsequent reabsorption of lamellipodium-like protrusions by cells, originating ECM-containing vacuoles, and/or degeneration stages characterized by the appearance of GA-CB-S-reactive, organule-derived dense bodies and progressive dissolution of all cell membranes. In one-week-implants, the first PPL-lined cells were found to co-exist with cells where GA-CB-S-reactive material accumulated, or exudated towards their edges, or outcropped at the ECM milieu, so acquiring PPL features. PPL-derived material was observed increasingly to affect the ECM on thin sections of one-week- to six-week-implants. These results show an endogenous source for PPLs and reveal that a peculiar cascade of cell degenerative steps is associated with valve mineralization in the subdermal model, providing new useful parameters for more reliable comparison of this experimental calcification process versus the physiological and pathological processes.

Animals↗
PubMed2005

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Disease Susceptibility↗
PubMed2003

Isolation of intact aortic valve scaffolds for heart-valve bioprostheses: extracellular matrix structure, prevention from calcification, and cell repopulation features.

Extracellular matrix (ECM) scaffolds isolated from valvulated conduits can be useful in developing durable bioprostheses by tissue engineering provided that anatomical shape, architecture, and mechanical properties are preserved. As evidenced by SEM, intact scaffolds were derived from porcine aortic valves by the combined use of Triton X-100 and cholate (TRI-COL) or N-cetylpyridinium (CPC) and subsequent nucleic acid removal by nuclease. Both treatments were effective in removing most cells and all the cytomembranes, with preservation of (1) endothelium basal membranes, (2) ECM texture, including the D-periodical interaction of small proteoglycans with normally D-banded collagen fibrils, and (3) mechanical properties of the treated valves. Ultrastructural features agreed with DNA, hexosamine, and uronic acid biochemical estimations. Calcification potential, assessed by a 6-week rat subdermal model, was significantly reduced by TRI-COL/nuclease treatment. This was not true for CPC only, despite better proteoglycan preservation, suggesting that nucleic acids also are involved in calcification onset. Human fibroblasts, used to repopulate TRI-COL samples, formed mono- or multilayers on surfaces, and groups of cells also were scattered within the valve leaflet framework. A biocompatible scaffolds of this kind holds promise for production of durable valve bioprostheses that will be able to undergo probable turnover and/or remodeling by repopulating recipient cells.

Animals↗
PubMed2003

Malachite green and phthalocyanine-silver reactions reveal acidic phospholipid involvement in calcification of porcine aortic valves in rat subdermal model.

Subdermal implant models are helpful in the study of calcification "in vivo" and for testing anticalcific treatments. After implantation of porcine aortic valve leaflets in rat subcutis, we previously found that glutaraldehyde-Cuprolinic blue reactions (GA-CB) at low pH induce favourable tissue unmasking from mineral deposits, and visualize peculiar, electrondense layers that outline the calcifying cells and matrix vesicle-like structures. The layer-forming material seemed to consist of acidic phospholipids because of its anionic nature and differential susceptibility to chemical/enzymatic extractivity. In the present investigation, pre-embedding glutaraldehyde-Malachite green (GA-MG) reactions and subsequent osmium post-fixation were compared with pre-embedding GA-CB reactions, combined with post-embedding von Kossa silver staining (GA-CB-S), to assess whether the layer-forming material is actually composed of acidic phospholipids and exhibits calcium-binding properties. After lowering standard pH, GA-MG reactions also caused sample demineralization and the appearance of pericellular osmium-MG-reactive layers comparable to CB-reactive ones. Moreover, GA-CB-S reactions showed that major silver precipitation was superimposed to the CB-reactive layers, whereas minor metal extra-precipitation occurred at three distinct, additional sites. These results demonstrate that a unique process of cell degeneration occurs in this calcification model, in which acidic phospholipids accumulate at cell surface, replacing cell membrane and acting as major apatite nucleator. However, the overall observations are consistent with the hypothesis that certain phases are common to the various types of normal and/or abnormal calcification.

Animals↗
PubMed2002

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5' regulatory region.

Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position -1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5' flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibility.

5' Flanking Region↗
PubMed2002

Novel ultrastructural features as revealed by phthalocyanine reactions indicate cell priming for calcification in subdermally implanted aortic valves.

The roles played by various determinants in physiological, pathological or experimental calcification are still unclear. In this investigation, new insights were gained into structural changes occurring in porcine aortic valves undergoing mineralization in the rat subdermal model and then subjected to reactions with cationic phthalocyanines (PHTs), at salt-critical electrolyte concentrations (CEC). PHT reactions showed decalcifying effects, depending on both acidic pH in the media employed and mineral substitution by Cuprolinic Blue (CB) itself, as well as specific reactivity which enabled the ultrastructural detection of unusual, PHT-positive layers (PPLs) encircling cells and matrix vesicles, at 0.05 M CEC conditions. Other reactions at different CEC conditions, or subsequent to enzymatical or specific extractive treatments, suggest PPL appearance is due to PHT uptake by clustered anionic phospholipids, which seem to be involved in mineral precipitation. PPLs present as a novel, reliable ultrastructural parameter indicating cell propensity in priming experimental and, possibly, pathological calcification.

Animals↗
PubMed2000

A model for type II collagen fibrils: distinctive D-band patterns in native and reconstituted fibrils compared with sequence data for helix and telopeptide domains.

The periodical D-band pattern is generally considered a unique ultrastructural feature shared by all fibril-forming collagens, which correlates with the intrafibril, paracrystalline array of tropocollagen monomers. Distinct band patterns have been reported, however, for collagen stained long-spacing (SLS) crystallites of genetic types I, II, and III. Moreover, D-band patterns of negatively stained, native type II collagen fibrils were found to be not identical to those of type I in our previous research. Because of (a) these distinctive features, (b) tropocollagen heterotrimeric conditions (type I) vs homotrimeric conditions (type II), and (c) different lengths and poor homology between extrahelical telopeptides, the molecular array or telopeptide conformation within the extensively studied type I collagen fibrils could be not the same as those in the very much less intensively studied type II collagen fibrils. In this investigation, a distinctive positive-staining D-band pattern was found for type II collagen fibrils obtained from human cartilages. A fibril model was developed by analyzing actual D-band patterns, and matching them against simulated patterns based on the primary structure of extrahelical and helical domains in human type II tropocollagen. In particular, a more prominent b(1) band was apparent in native type II collagen fibrils than in type I. This distinctive feature was also observed for native-type collagen fibrils reconstituted from purified type II collagen, i.e., free from associated minor type XI collagen. On modeling possible monomer arrays, the best fit between microdensitograms and simulation traces was found for 234 amino acid staggering, as is also the case for type I collagen fibrils. On comparing this model with an analogous one for type I collagen fibrils, there was a higher intraband distribution of charged residues for band b(1), consistent with the higher electrondensity observed for this band in type II collagen fibrils. N- and C-telopeptide displacement in the model corresponded to D-locations of a c(2) subband, which we named c(2.0), and band a(3), respectively. In simulation profiles, c(2.0) -like and a(3) -like peaks mimicked the corresponding peaks in microdensitograms when molecular reversals were adopted at positions 10N-12N, 12C-14C, and 17C-19C for N- and C-telopeptides. Hydrophobic interactions and algorithmic predictions of protein secondary structure, according to Chou and Fasman and Rost and Sander criteria, were consistent with these conformational models, and suggest that an additional molecular reversal may occur at positions 3N-5N. These telopeptide "S-fold" conformations, interpreted as axial projections of tridimensional conformation, may represent starting points for further investigation into the still unresolved tridimensional conformation of telopeptides in monomers arrayed within type II collagen fibrils.

Amino Acid Sequence↗
PubMed2000

[Human olfactory mucosa biopsy with endoscopic technique: clinical and structural observations on neurosensory epithelium rearrangement].

Optical and electron microscopy have been widely used to study the structural features of olfactory epithelium in several Vertebrate species. To date, however, understanding of histopathological alterations in the human olfactory neuroepithelium has been quite limited due to the difficulty in obtaining well preserved, intact fragments of mucosa. The recent introduction of endoscopic biopsy techniques has made it possible to analyze this epithelium in greater detail. In the present work, endoscopic biopsy has been performed on samples from 10 rhinologically healthy subjects. The technique used proved quite simple and did not present any risks or complications. Moreover, all samples were well preserved, as confirmed by histology. In addition, the histological pictures suggest that normal rearrangement of neuroepithelium is not an uniform process but takes place following a zone pattern with distinct dynamics between neurosensorial and support cells. Greater diffusion of this technique would not only make it possible to use different techniques to gain more detailed knowledge of tissue structure, ultrastructure and dynamics in human neuroepithelium, but it would also provide improved diagnostic and forensic evaluation in cases of anosmia, disosmia and hyposmia.

Adult↗
PubMed1999

The sacrospinous vaginal vault suspension: Critical analysis of outcomes.

One hundred and three women with a preoperative diagnosis of a pelvic support defect underwent right sacrospinous fixation of the vaginal apex. The procedure was performed either therapeutically (in 63 subjects with vaginal vault eversion) or prophylactically (40 patients with severe uterovaginal prolapse), and was associated with other reconstructive procedures to repair the coexisting cystocele, enterocele or rectocele. Preoperative and postoperative assessments of each vaginal site were compared and the results in the cure of stress urinary incontinence, if present, were evaluated with regard to the type of surgery performed. The overall rate of satisfactory results in the repair of the superior vaginal defect was 94%, and good anatomic results were achieved in the repair of either enterocele or rectocele. Conversely, the repair of the anterior vaginal wall was not as good as in the posterior and superior vaginal sites. Stress urinary incontinence was successfully managed in 72% of the women using different anti-incontinence procedures.

Adult↗
PubMed1997

Dietary habits, reproductive and menstrual factors and risk of dysmenorrhoea.

In order to analyze risk factors for dysmenorrhoea, we conducted a case-control study. Cases were 106 women (median age 27 years) with moderate or severe dysmenorrhoea lasting 12 months or more. Controls were 145 women (median age 26 years) without dysmenorrhoea, admitted for routine gynecological examination at the outpatient gynecological services of the same clinic where cases had been identified. In comparison with women reporting short menstrual cycles (every 25 days or less) the relative risk (RR) of dysmenorrhoea was 2.0 and 2.6, respectively, in those reporting their menstrual cycles of 26-30 days and of 31 days or more, and the RR was 3.6 (95% confidence interval (CI): 1.0-13.4) for women reporting totally irregular menstrual cycles. The estimated RRs were, in comparison with women reporting menstrual flows lasting 4 days or less, respectively 2.2 and 1.9 in those reporting menstrual flows lasting 5 and 6 days or more. Fourty-four (58%) cases but only seven (5%) controls reported heavy menstrual flows (RR in comparison with women reporting slight or normal menstrual flow 12.6, 95% CI: 5.0-32.1). As regards dietary factors, no associations emerged between the various food items, with the exception of cheese and eggs, which tended to be more frequently consumed by cases than controls. The results of this study suggest that the risk of dysmenorrhoea is higher in women with irregular, long and heavy menstrual flows. No association emerged between reproductive history and dysmenorrhoea. Likewise, no clear relationship emerged between intake of several dietary factors and risk dysmenorrhoea.

Adult↗
PubMed1996

Vaginal cabergoline in the treatment of hyperprolactinemic patients intolerant to oral dopaminergics.

OBJECTIVE: To evaluate the effectiveness and tolerance of vaginal cabergoline in hyperprolactinemic patients intolerant to oral dopaminergics. DESIGN: Case reports. SETTING: University hospital endocrinological outpatient clinic. PATIENTS: A 35-year-old primipara woman with idiopathic hyperprolactinemia and a 22-year-old female with primary amenorrhea harboring macroprolactinoma. INTERVENTIONS: Treatment with vaginal cabergoline (0.5 mg two and five times a week). MAIN OUTCOME MEASURES: The serum PRL levels and side effects were assessed before and during treatment. RESULTS: A single vaginal dose of 0.5 mg cabergoline reduced serum PRL levels by approximately 50% to 85% of basal values over a period of 4 to 5 hours. In the patients with idiopathic hyperprolactinemia, serum PRL levels normalized during long-term treatment, whereas in the one with macroprolactinoma they remained above the normal values (79 ng/mL [conversion factor to SI unit, 3.180]) despite resumption of menses and marked tumor shrinkage (70% reduction). No side effects were reported. CONCLUSIONS: Vaginal cabergoline is a safe and effective method of therapy for hyperprolactinemia and it avoids the adverse events of oral administration.

Adult↗
PubMed1996

Residual uterine septum of less than 1 cm after hysteroscopic metroplasty does not impair reproductive outcome.

The objective of this study was to ascertain if incomplete correction leaving a residual uterine septum of < or = 1 cm affects fertility outcome. Reproductive outcome in 17 women with a residual septum of between 0.5 cm and 1 cm after hysteroscopic metroplasty was compared to that in 51 women with no residual septum or one of < 0.5 cm. Septal lysis was performed with microscissors or resectoscope. One month after operative hysteroscopy, abdominal ultrasonography was performed on all the women and those with a residual septum of > 1 cm then underwent a second operative hysteroscopy to complete the lysis. The cumulative pregnancy and birth rates were calculated and the curves compared using the log-rank test. The cumulative 18 month probability of becoming pregnant was 44.5% in the patients with residual septum and 52.7% in those with no residual septum (not significantly different), and the cumulative 18 month probability of giving birth to a child was 27.5 and 36% respectively (also not significant). The presence of a residual uterine septum of between 0.5 and 1 cm as shown by ultrasonography appears not to worsen the reproductive prognosis compared with that in women in whom the septum has been completely or almost completely corrected.

Abortion, Habitual↗
PubMed1996

Carboplatin monochemotherapy in elderly patients with nonoperable transitional cell carcinoma of the bladder: a two-stage, phase II study.

Elderly patients with nonoperable transitional cell carcinoma of the bladder need a rather active, but less toxic treatment than full-dose polychemotherapy. This study was designed to determine whether the cisplatin-analogue carboplatin (which is less nephrotoxic and less neurotoxic than the parent compound) has sufficient activity against T2-T4 neoplasms (both nonmetastatic and metastatic) to warrant further development in phase III trials. Carboplatin dose was adjusted according to creatinine clearance, with a maximum dose of 300 mg/m2. The patient selection for this screening for activity was adjusted by the use of the 'optimal' two-stage design. Seventeen patients were enrolled, with a median age of 78 years (range: 70-85), a median performance status of 80% (range: 70-90%); 13 patients were lymph node-negative (10 T2, 2 T3, 1 T4) and 4 had locoregional or distant node metastases. Nine patients had a complete response (3 in the first, 9-patient, stage, and 6 in the second, 8-patient, stage), demonstrating that carboplatin had sufficient activity (at the 'desirable' target level of 35%); almost all responses were observed in T2 patients. Six patients had stable disease, and 2 had disease progression during treatment. The toxicity was acceptable, with only 41% of patients having grade II-III hematologic toxicity. More than 30% of patients were estimated to be free from progressive disease (54% alive) at 24 months. In our opinion carboplatin is suitable to be tested-in a phase III testing versus full-dose radiation therapy-as adjuvant after initial transurethral resection of the prostate in elderly patients with T2 transitional cell carcinoma of the bladder considered radically nonoperable for medical problems.

Aged↗
PubMed1996

Ultrastructural aspects of endometrium in infertile women with septate uterus.

OBJECTIVES: To evaluate the endometrial surface morphology in patients with septate uterus and primary infertility in an attempt to throw light on the question of whether endometrial anomalies are involved in the pathogenesis of infertility in women with mullerian malformations. DESIGN: Endometrial biopsies were performed in eight women with septate uterus and primary infertility during hysteroscopy scheduled in the preovulatory phase of the cycle (when a follicle > 17 mm was identified by ultrasonography and E2 levels were >200 pg/mL [conversion factor to SI unit, 3.671]). Two samples were obtained from each patient, one from endometrium covering the septum and the other from endometrium lining the lateral wall of the uterus. All specimens were examined by scanning electron microscopy. MAIN OUTCOME MEASURES: The number of glandular ostia, the ciliated:nonciliated cell ratio, and the number of cilia on ciliated cells were analyzed in endometrial specimen from both the covering of the septum and the corresponding uterine lateral wall. RESULTS: In five patients septal endometrium showed the following defective preovulatory changes with respect to endometrium of the lateral uterine wall: a reduced number of glandular ostia, irregular nonciliated cells with rare microvilli, incomplete ciliogenesis on ciliated cells, and decrease in the ciliated:nonciliated cell ratio (1:52 +/- 11 versus 1:21 +/- 8). CONCLUSIONS: Our results indicate a decrease in the sensitivity of endometrium covering the septa of malformed uteri to preovulatory hormonal changes. This could play a role in the pathogenesis of primary infertility in patients with septate uterus.

Adult↗
PubMed1996

Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study.

OBJECTIVE: To assess whether intrauterine insemination (IUI) improves the fertility rates in women with unexplained infertility. STUDY DESIGN: We recruited 68 women with unexplained infertility and allocated them randomly to treatment with three to five cycles of superovulation plus IUI (36 patients) or superovulation alone (32 patients). Superovulation was obtained with clomiphene citrate, human menopausal gonadotropins and human chorionic gonadotropins. RESULTS: The cycle fecundity rate was 10% in patients who underwent superovulation alone and 19% in those treated with superovulation plus IUI (P < .05). CONCLUSION: Our results demonstrate that superovulation plus IUI is more effective than superovulation alone in the treatment of unexplained infertility.

Adult↗
PubMed1995

Mitogen-induced lymphocyte proliferation and peripheral blood mononuclear cell beta-endorphin concentrations in primary dysmenorrhoea.

Dysmenorrhoea is a recurrent painful disease which causes physical and psychological stress. The purpose of the present study was to investigate whether there was a measurable derangement of immune cells and immune responses in women with severe primary dysmenorrhoea. On day 26 of one cycle and on days 1 and 3 of the following cycle we measured polyclonal, mitogen-induced lymphocyte proliferation and beta-endorphin concentration in peripheral blood mononuclear cells obtained from 16 infertile women with normal pelvis, of whom eight had and eight did not have the disorder. In women with dysmenorrhoea, polyclonal mitogen-induced lymphocyte proliferation was lower than in controls on all 3 days considered, but the difference was statistically significant only on day 26 (43,605 +/- 9876 micrograms/ml versus 67,305 +/- 15,249 micrograms/ml; P < 0.01). Monocyte beta-endorphin concentrations in the patients with dysmenorrhoea were significantly elevated on day 3 compared to controls (67.8 +/- 24.3 pg/10(6) cells versus 29.7 +/- 6.9 pg/10(6) cells; P < 0.05). Our results demonstrate that immune responses are modified in patients with primary dysmenorrhoea. These effects are independent of circulating hormone concentrations and are consistent with the role of dysmenorrhoea as a stressful event.

Adult↗