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Biomedical subjects

P Puddu

Publications and source records attributed to P Puddu.

At least 91 records · Page 5Linked to original sources
PubMed1997

T-helper 2 involvement in the pathogenesis of bullous pemphigoid: role of soluble CD30 (sCD30).

Bullous pemphigoid (BP) is an autoimmune blistering skin disease in which autoantibodies are directed against hemidesmosomal proteins of basal keratinocytes. The presence of activated T helper cells in lesions and peripheral blood of BP patients, the eosinophilia, the high levels of serum IgE, eosinophil cationic protein and soluble immune products such as IL-2, sIL-2R, IL-5, soluble CD23 (sCD23) strongly suggest the involvement of a cell-mediated immune reaction in which Th2 lymphocytes could play a pivotal role. To seek evidence to support this hypothesis we evaluated serum levels of IL-4 and sCD30, a specific activation marker of cells able to produce Th2-like cytokines, in 25 patients affected with BP. Serum from both healthy donors and pemphigus vulgaris (PV) patients were used as controls. Our results demonstrated significantly higher levels of IL-4 and sCD30 in patients with BP in relation to both normal individuals (16.6 +/- 7.9 vs 4.5 +/- 2.2 pg/ml, P < 0.0001; 30.3 +/- 10 vs 10.5 +/- 4 U/ml, P < 0.0001) and PV patients (6.2 +/- 4 pg/ml, P < 0.0001; 16 +/- 8.5 U/ml, P < 0.0001). Furthermore, a positive correlation between IL-4 and sCD30 was found (R = 0.85, P < 0.0001). In a subset of seven patients observed after systematic immunosuppressive therapy, we detected a significant reduction in sCD30 serum level (36.9 +/- 7.3 vs 16.3 +/- 6.8 U/ml, P = 0.002), with a parallel improvement in their clinical condition. These results seem to be consistent with the systematic involvement of Th2 lymphocytes in the pathogenesis of BP and suggest a role for sCD30 as a serological marker of disease activity.

Aged↗
PubMed1997

Neutrophilic figurate erythema of infancy.

We describe a transient figurate erythema in an 11-month-old female infant with a 2-month history of arcuate and annular erythematous lesions localized on the face, trunk, and limbs. Constitutional symptoms were absent. Previous medical history was unremarkable. Full blood examination, erythrocyte sedimentation rate, antistreptolysin-O titer, anti-Ro, and anti-La antibodies were within normal limits or negative. Histologic examination revealed a superficial and deep perivascular and interstitial dermatitis constituted mostly of neutrophils and abundant nuclear dust. The lesions resolved spontaneously within a few months without scarring or atrophy. Recurrence has not occurred. This case suggests that figurate erythemas in infants rarely may disclose a neutrophilic histologic pattern, which must be differentiated from that of other neutrophilic dermatoses.

Antibodies, Antinuclear↗
PubMed1997

[Italian clinical cardiology research at the international level. Statistical data from the period 1983-1993].

Recent studies show that, among advanced countries, the rank of cardiological research finds Italy last for number of scientific publications and for gross expenditure on research and development. To assess more thoroughly the characteristics of Italian clinical cardiological research we examined, over the period 1983-1993, all original articles published by five important international cardiology journals (Circulation, American Heart Journal, American Journal of Cardiology, Journal of the American College of Cardiology and European Heart Journal). During the mentioned period the Italian contribution (743 articles over a total of 16375, mean prevalence of 4.5%) has increased from 3% in 1983-1985 to 5.8% in 1991-1993 (p < 0.0001). Taking into account that research often results from the joint-work of different centers, the 743 articles derived from 1056 contributions from just over 120 centers. Of these contributions 57% were from universities, 23% from hospitals, 19% from research institutes, and 1% from private foundations. The cooperation with foreign countries has steadily increased, particularly with the USA (45%) and with the European nations (42%). Within the first three names, the contribution of female Authors has increased from 7% in 1983-1985 to 16% in 1991-1993 (p = 0.0001). The mean prevalence of female Authors as last name was 4% and did not change with time. As to geographic distribution, 57% of the scientific publications comes from the North, 28% from the Centre, and 15% from the South. After adjusting these data for population size, the percentages were respectively 40, 46, and 14%. An index of productivity (the ratio between the number of scientific contributions from universities and research institutes and their funding) was highest in the North. The Italian scientific contribution to international cardiological research is not satisfactory, although it is significantly increasing; yet, this trend might worsen due to the shortage of funding. The collected data outline that in the three main national geographic areas, the distribution of funds and scientific productivity are markedly unbalanced.

Cardiology↗
PubMed1997

[Ehlers-Danlos syndrome type I. Ultrastructural study].

Ehlers-Danlos syndrome comprises a very heterogeneous group of collagen diseases characterised in clinical terms by fragility and cutaneous hyperextensability, ligamentous hyperlaxity, ecchymosis, scarring, visceral and neurological manifestations. Having been described in detail by Ehlers in 1899 and Danlos in 1908, it was subsequently classified into various clinical types. At present at least 11 forms are recognised on the basis of their clinical characteristics, methods of transmission and biochemical defect; the first four types of the syndrome account for approximately 95% of cases. Almost all forms are transmitted with a dominant autosomic character. Specific genetic mutations have been ascertained whereas the biochemical defect has been identified in numerous types. Ehlers-Danlos type 1 syndrome is the most frequent and most severe form. The biochemical anomaly underlying the altered deposition of collagen fibre is still unknown and this is responsible for the "storiform" appearance of collagen fibre on ultrastructural examination. The authors have described a typical case of "Ehlers-Danlos type 1 syndrome" in which the diagnosis was confirmed by comparing clinical data and the results of ultrastructural tests which revealed the characteristic "pattern" of collagen fibres.

Adolescent↗
PubMed1997

[Cardiac pacemaker and radiotherapy: a growing association. Report of a clinical case].

Cardiac pacing is increasingly common. In 1986, in the USA there were more than 500,000 pacemaker-implanted patients and at least 100,000 new pacemaker implants were performed, for a total of 3,000 pacemakers for million inhabitants. The increment in cardiac pacing is due to: a fall in cardiovascular mortality; increased elderly population, in which bradyarrhythmias are frequent; and the introduction of implantable cardioverter defibrillators (ICD). In 1992, in Italy, there were 30,500 deaths due to lung tumours and 10,900 deaths for breast malignancies. Both malignancies are more common in patients older than 65. Lung and breast cancer therapy involves the use of surgery, radiation, or chemotherapy, and often a combination of two or all three. In particular 40% of cancers are managed with radiotherapy. It is therefore likely that cancer patients may require radiotherapy at sites (lung, breast) where a pacemaker is implanted. The authors describe the finding on a chest radiogram of a one centimeter nodular mass at the right superior lobe almost completely hidden by the pacemaker. The modalities to proceed to radiotherapy, without damaging the sensitive pacemaker, are discussed.

Aged↗
PubMed1996

A common insertion mutation in COL7A1 in two Italian families with recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermis bullosa is ultrastructurally characterized by the absence of anchoring fibrils, and genetic analyses have revealed that recessive dystrophic epidermolysis bullosa results from mutations in the type VII collagen gene (COL7A1). The mutations disclosed thus far are largely family specific, with no evidence for mutational hotspot(s). In this study, we report a recurrent premature termination codon mutation detected in two apparently unrelated Italian families in different regions of the country. This mutation, 497insA in exon 4 of COL7A1, was found in combination with two different premature termination codon mutations in these families. Haplotype analysis suggested a shared genetic background in the allele containing the mutation 497insA, suggesting that this genetic lesion may represent an ancestral mutation within the Italian gene pool.

Adult↗
PubMed1996

Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: requirement of gamma interferon for IL-12 secretion.

We studied the effects of the gp120 glycoprotein of human immunodeficiency virus type 1 on the expression of interleukin-12 (IL-12) in human monocytes and in monocyte-derived macrophages. Induction of the mRNA for both the p35 and p40 subunits of IL-12 was observed in both cell types after gp120 treatment. We then evaluated cytokine secretion by using an enzyme-linked immunosorbent assay which recognizes only the IL-12 heterodimer. No IL-12 was detected in monocytes/macrophages treated with gp120 alone. A consistent IL-12 secretion was found in macrophages primed with gamma interferon (IFN-gamma) and subsequently treated with gp120. Low levels of IL-12 were occasionally observed in IFN-gamma-primed monocytes stimulated with gp120. The greater response of macrophages than of monocytes to the priming effect of IFN-gamma was consistent with the finding that IFN-gamma induced a much stronger antiviral state to vesicular stomatitis virus in macrophages than in monocytes. These data indicate that gp120 is an inducer of IL-12 expression in monocytes/macrophages and that IFN-gamma is an essential cofactor for IL-12 secretion, especially in differentiated macrophages.

Base Sequence↗
PubMed1996

Three-dimensional distribution of basement membrane components in dystrophic recessive epidermolysis bullosa.

Absent or defective collagen VII at the dermo-epidermal junction is the hallmark of dystrophic recessive epidermolysis bullosa. Little is known of the alterations of other collagenous and non-collagenous components of the basement membrane; it is likely that their assembly may be disturbed by the lack of collagen VII molecules. The spatial relationship of collagen IV and laminin has been studied, both in bullous and in non-bullous areas. Skin biopsies from five patients affected by severe dystrophic recessive epidermolysis bullosa were rapidly frozen and freeze-dried. Collagen IV and laminin were labelled with specific monoclonal antibodies and FITC- or TRITC-conjugated secondary antibodies. Sections were observed with conventional light/fluorescence microscopy and with confocal laser scanning microscopy. Collagen IV and laminin were not co-localized: the former displayed a split image, being present at the floor and the roof of the blister, while the latter was confined to the roof. Confocal microscopy also allowed three-dimensional (3D) reconstruction of the dermo-epidermal junction from a series of optical sections, with viewing of the reconstructed specimen from a sequence of angles. By this procedure, laminin exhibits an irregular, coarsely granular distribution, both in affected and in apparently non-affected areas, while collagen IV appears as a homogeneous sheet. These results show that freeze-drying is the technique of choice for high-resolution immunofluorescence of skin samples and suggest that in dystrophic recessive epidermolysis bullosa, a complex disruption of the extracellular matrix assembly exists even before blister formation, probably due to the lack of collagen VII.

Basement Membrane↗
PubMed1995

Relation of severity of symptoms to transient myocardial ischemia and prognosis in unstable angina.

OBJECTIVES: This study was undertaken to compare the relative power of the severity of angina versus that of any other clinical, electrocardiographic (ECG) and angiographic findings in predicting the risk of subsequent in-hospital coronary events in patients admitted to the coronary care unit for treatment of unstable angina. BACKGROUND: The presence or absence of chest pain has traditionally been used to guide management and therapy of unstable angina. However, recent studies raised the possibility that the cumulative duration of ischemia may be an additional index of prognosis. METHODS: We studied 104 consecutive patients admitted to the coronary care unit because of unstable angina. Diaries of symptoms were accurately kept. All patients underwent Holter ambulatory ECG monitoring during the 1st 24 h and angiography within 1 week of admission. RESULTS: During the hospital stay, 41 patients (group 1) had subsequent coronary events; the remaining 63 patients (group 2) had a good clinical outcome. Recurrence of chest pain after admission was observed in 76% of patients: 36 of the 41 group 1 patients (sensitivity 88%) and 43 of the 63 group 2 patients (specificity 32%). Anginal scores (frequency and persistence of pain, duration of each single episode and pain-free interval) showed high specificity but low sensitivity for detecting evolution toward subsequent coronary events. On Holter monitoring, the duration/24 h of the total number of ischemic episodes was consistently greater in group 1 than in group 2. A cumulative duration of ischemia > or = 60 min/24 h was observed in 34 of the 41 group 1 patients (sensitivity 83%) but in only 16 of the 63 group 2 patients (specificity 75%). High risk coronary artery lesions (left main coronary artery disease or complex stenosis) were detected in 36 of the 41 group 1 patients and in 26 of the 63 group 2 patients. CONCLUSIONS: Transient myocardial ischemia detected by Holter monitoring, but not chest pain, is the best predictor of unfavorable short-term clinical outcome. The decision to perform early angiography and revascularization cannot be based on symptoms alone.

Aged↗
PubMed1995

Association of serum C3 levels with the risk of myocardial infarction.

PURPOSE: Serum complement and IgA levels have been found to be retrospectively associated with the presence of diffuse atherosclerosis. This study was performed to assess whether serum immunoglobulins and complement components are predictive of future ischemic events. PATIENTS AND METHODS: The baseline values of IgG, IgA, IgM, C3, and C4 were measured in the sera from a cohort of 860 inhabitants of the town of Brisighella, Italy. They were 444 men and 416 women, mean age 53.9 years (SD 12.4, range 23 to 84), who had not had any ischemic events (myocardial infarction [MI], angina pectoris, stroke, transient ischemic attack, or intermittent claudication) at the time of blood sampling in 1984. Their baseline values for the main recognized risk factors for atherosclerosis were known at baseline and for 4 years of follow-up. Multiple logistic regression analysis was performed for associations between ischemic events and immunologic variables (including serum IgG, IgA, IgM, C3, and C4) and risk factors for atherosclerosis (including age, sex, diastolic blood pressure, cigarette consumption, Quetelet index, total cholesterol, HDL cholesterol, triglycerides and blood glucose). RESULTS: During follow-up, 57 subjects experienced ischemic events, including 28 cases of coronary heart disease (17 MI and 11 angina pectoris). Of the immunologic variables studied, only serum C3 was found to be independently associated with ischemic events (P < 0.005 for any ischemic events, coronary heart disease, and MI). The population was divided into thirds according to C3 values. The cumulative incidence of MI was 7.1/1,000 in the low third, 10.6/1,000 in the middle third and 40.8/1,000 in the high third (risk ratio for high versus middle plus low = 4.2 after adjustment for age and sex; 95% CI 1.5 to 11.7). A separate analysis for the sexes showed that serum C3 was a particularly powerful predictor of MI in men. Men whose C3 levels were in the top third had a 72.6/1,000 incidence of MI while the incidence in the rest of the male population was 6.2/1,000 (risk ratio 10.7 after adjustment for age; 95% CI 2.3 to 49.0). When similar analyses were performed for angina pectoris, stroke, and intermittent claudication, no significant increase in risk was found to be associated with serum C3. CONCLUSION: C3 levels measured in sera from male subjects without previous ischemic events are independently associated with the risk of MI.

Adult↗
PubMed1995

Induction of interleukin-10 by human immunodeficiency virus type 1 and its gp120 protein in human monocytes/macrophages.

In this study, we evaluated the effects of human immunodeficiency virus type 1 (HIV-1) and its gp120 protein on interleukin-10 (IL-10) expression in cultured human monocytes/macrophages. Infection of either 1-day monocytes or 7-day monocyte-derived macrophages with HIV-1 strain Ba-L resulted in clear-cut accumulation of IL-10 mRNA at 4 and 24 h. Likewise, treatment of these cells with recombinant gp120 induced IL-10 mRNA expression and caused a marked increase in IL-10 secretion. Monoclonal antibodies to gp120 strongly inhibited recombinant gp120-induced IL-10 secretion by monocytes/macrophages. Moreover, the addition of IL-10 to monocytes/macrophages resulted in a significant inhibition of HIV-1 replication 7 and 14 days after infection. On the whole, these results indicate that HIV-1 (possibly through its gp120 protein) up-regulates IL-10 expression in monocytes/macrophages. We suggest that in vivo production of IL-10 by HIV-primed monocytes/macrophages can play an important role in the early response to HIV-1 infection.

Base Sequence↗
PubMed1995

[Serum C3 as a screening factor in the primary prevention of myocardial infarct].

This study addresses the possible use of serum C3 (third component of the complement system) to select the subjects to be submitted to diet or drug therapy in the primary prevention of myocardial infarction. C3 is synthesized by macrophages, which are the main cells involved in atheroma formation, and an association between serum C3 and the risk of myocardial infarction has recently been found in the male sex. We have studied 332 men aged 45-75 years, who had no cardiovascular disease at any time before blood sampling. In their sera C3 measurement was performed by nephelometry. The 4 year follow-up was known for all of these subjects: in particular, 11 had a myocardial infarction. The average LDL cholesterol (LDL-C) levels in the whole population were rather high (162.2 +/- 45.8 (1 SD) mg/dl). As standard treatment criteria (A), those suggested for primary prevention by the National Cholesterol Education Program panel of experts were adopted: diet if LDL-C > or = 160 mg/dl, or LDL-C > or = 130 mg/dl + 2 additional risk factors; drugs if, after diet, LDL-C > or = 190 mg/dl, or LDL-C > or = 160 mg/dl + 2 risk factors. This scheme was compared with two models of treatment which included the measurement of serum C3. According to the first of such models (B), diet should be prescribed when C3 levels are within the high third of distribution (> or = 135 mg/dl) with LDL-C > or = 100 mg/dl, and drugs should be given if, after diet, serum C3 is > or = 135 mg/dl with LDL-C > or = 130 mg/dl. The second model based on C3 (C) is of combined type since, in addition to model B criteria, it also suggests to prescribe a diet if LDL-C > or = 190 mg/dl, while drugs should be given if, after diet, LDL-C levels persist > or = 190 mg/dl. The effect of diet has been simulated by assuming a 10% decrease in LDL-C levels. According to all of these criteria, the subjects to treat with diet with the models A, B and C would have been, respectively, 71, 27 (p < 0.0001 vs mod A) and 45% (p < 0.0001 vs mod A) of the whole population, including among them, respectively, 82, 82 and 100% of the future myocardial infarctions. After diet, according to the three models A, B and C -29, 20 (p = 0.0117 vs mod A) and 30% of the whole population should have been treated with drugs, including, respectively, 54, 64 and 82% of the future myocardial infarctions. In conclusion, the use of criteria based on serum C3, with respect to more traditional guidelines, might allow a more precise identification of the subjects to submit to diet and drug treatment in the primary prevention of myocardial infarction.

Aged↗