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Biomedical subjects

P Puddu

Publications and source records attributed to P Puddu.

At least 55 records · Page 3Linked to original sources
PubMed2000

Mortality rates and number of deaths from cardiovascular diseases in Italy from 1982 to 1993. A comparison with total and tumour data.

In this study the recent Italian trends in cardiovascular deaths and mortality are described and compared with the trends regarding total and tumour deaths and mortality. The data, collected from the National Institute of Statistics, are presented as total (T), tumour (TU), cardiovascular (CV), cerebrovascular (CVD), ischemic heart disease (IHD) standardized mortality (sm), non-standardized mortality (nsm) and absolute number of deaths (d), according to sex, age, and geographical area. Data on sm were available only for the age group <75 years old. In males, from 1982 to 1993, T-sm fell by 18%, TU-sm by 4%, CV-sm by 30%, CVD-sm by 38% and IHD-sm by 24%. In females, the decrements were generally greater: T-sm 20%, TU-sm 4%, CV-sm 35%, CVD-sm 39% and IHD-sm 28%. Since 1985/87, tumours have been the leading cause of mortality, in both sexes. By 1991/93, the highest rates of CV, CVD, IHD-sm were reported mostly in the South of Italy. Non-standardized mortality rates for tumours increased, and for cardiovascular diseases decreased, in both sexes and age groups (<75 and >/=75 years old). As for sm, in the group <75 years, old tumours have been the leading cause of mortality since 1985/87, but in the older age group CV-nsm has been more than twice TU-nsm. By 1991/93 in comparison with 1982/84, CV deaths have fallen by 6% (-28% in the age group <75 years, +3% in the age group >/=75 years), while TU deaths have grown by 17% (+3% in the age group <75 years, +45% in the age group >/=75 years). Considering all age groups, by 1991/93 the absolute number of CV-d (239.241) was much greater than the number of TU-d (151.908); overall, almost 70% of CV-d and 40% of TU-d took place in the older age group. For the near future, the rapid aging of the Italian population (from 1982/84 to 1991/93 there was a 40% increment in the population older than 75 years) is a relevant variable to take into account. Thus, despite the 'reassuring' fall in CV-sm and nsm, cardiovascular diseases are expected to remain the major cause of death and physical disability in adults.

Adult↗
PubMed2000

Psychiatric morbidity in dermatological outpatients: an issue to be recognized.

BACKGROUND: There is a high prevalence of psychiatric disorders in dermatological outpatients. OBJECTIVES: To estimate the magnitude of this problem and to identify a set of variables associated with the presence of psychiatric disorder. METHODS: All adults attending the outpatient clinics of a dermatological hospital on predetermined days were given a questionnaire comprising the Skindex-29 and the 12-item General Health Questionnaire (GHQ-12). RESULTS: In total, 4268 questionnaires were given at admission, and 3125 were returned. Of these, 546 were blank or incomplete, leaving 2579 respondents (response rate 60.4%). Using a stringent cut-off threshold (> or = 5) for psychiatric case identification with the GHQ-12, scored in the conventional way, the overall prevalence of psychiatric morbidity was 25.2% (95% confidence interval 23.6-27.0%). We found a higher prevalence of psychiatric disorders in women and in widows/widowers, controlling for age. Health-related quality of life was a much stronger predictor of psychiatric morbidity than physician-rated clinical severity. High prevalence rates (> 30%) were observed among patients with acne, pruritus, urticaria, alopecia and herpesvirus infections, and in subjects without objective signs of dermatological disease. CONCLUSIONS: Our study has depicted the situation that is actually faced by dermatologists in their everyday practice, where they are in a unique position to recognize psychiatric morbidity and to take appropriate measures. The GHQ-12, being easy for patients to compile and for physicians or nurses to score, may be a practical tool to increase identification of patients with substantial psychological distress or formal psychiatric disorder in order to provide more comprehensive and appropriate intervention.

Adult↗
PubMed2000

Placenta growth factor is induced in human keratinocytes during wound healing.

Placenta growth factor (PlGF) is a dimeric glycoprotein, structurally and functionally related to the vascular endothelial growth factor, a potent angiogenic/permeability factor known to play a role in the neoangiogenesis during wound repair. In this study we evaluated the expression of PlGF in human keratinocytes and investigated its possible role in wound healing. Northern blot analysis on cultured keratinocytes revealed a 1.7 kb mRNA transcript and reverse transcriptase-polymerase chain reaction allowed the detection of two PlGF isoforms generated by alternative RNA splicing. PlGF and vascular endothelial growth factor homodimers as well as vascular endothelial growth factor/PlGF heterodimers could be detected in keratinocyte conditioned medium. Increased expression of both PlGF mRNA and protein was observed upon treatment of keratinocytes with epidermal growth factor, transforming growth factor-alpha, transforming growth factor-beta, and interleukin-6, all cytokines present at the wound site during the early phase of repair. The analysis of human full-thickness healing wounds revealed appreciable levels of PlGF mRNA and protein in the migrating keratinocytes starting from day 3 after injury, and increasing at day 5. At day 7 PlGF mRNA was no longer detectable, while the protein was still expressed by migrating suprabasal keratinocytes. At day 13, when the wound had reepithelialized, PlGF immunostaining was completely negative. By in situ hybridization an intense signal for PlGF was also found on endothelial capillaries adjacent to the wound. These data demonstrate that keratinocytes are a source of PlGF during wound healing in vivo and indicate a role for this factor in the neoangiogenesis process associated with cutaneous wound repair.

Angiogenesis Inducing Agents↗
PubMed2000

Nitric oxide inhibits cornified envelope formation in human keratinocytes by inactivating transglutaminases and activating protein 1.

Epidermal keratinocytes undergo terminal differentiation to form the stratum corneum, which consists of many layers of flat dead cells. These cells assemble an insoluble cornified envelope composed of specific proteins deposited on the intracellular surface of the cell membrane. The proteins are crosslinked by the action of transglutaminases, which catalyze the formation of isodipeptide bonds between the epsilon-NH2 side chain of a lysine residue and the gamma-amide side chain of a glutamine residue. Transglutaminases share a conserved, highly reactive cysteine in their active site. In this study, we found that nitric-oxide-releasing compounds inhibited cornified envelope formation in cultured keratinocytes and the in vitro crosslinking of loricrin, a natural substrate of transglutaminases. The NO donors inhibited transglutaminase catalytic activity in a dose-dependent manner, in both purified enzymes and keratinocyte extracts. Titration of thiol groups of transglutaminases indicated that NO regulates their enzymatic activity by chemically modifying a cysteine residue, possibly by S-nitrosylation. NO was also found to inhibit DNA-binding activity of activating protein 1 in keratinocyte nuclear extracts, and to interfere with the transactivation of activating protein 1 responsive genes such as transglutaminase 1, involucrin, and loricrin, whose expression is regulated during epidermal differentiation. In conclusion, we propose that NO may inhibit keratinocyte differentiation, acting both at transcriptional level (inactivation of activating protein 1) and at post-translational level (inhibition of transglutaminase activity).

Cross-Linking Reagents↗
PubMed2000

A mutation in the V1 domain of K16 is responsible for unilateral palmoplantar verrucous nevus.

Palmoplantar keratodermas are a group of heterogeneous diseases characterized by thickening, and marked hyperkeratosis, of the epidermis of the palms and soles. Palmoplantar keratodermas can be divided into four major classes: diffuse, focal, punctate, and palmoplantar ectodermal dysplasias. All forms are genetic diseases inherited as autosomal dominant disorders. We studied a patient exhibiting a localized thickening of the skin in parts of the right palm and the right sole, following Blaschko's lines, that does not fit into any classes already described. We sequenced the keratin 16 cDNA derived from skin biopsy material from affected and non affected palms. The keratin 16 cDNA sequence from lesional epidermis showed a 12 base pair deletion (309-320del), which deletes codons 104-107. The mutation is predicted to delete four amino acids, GGFA, from the V1 domain of the keratin 16 polypeptide, close to the 1A domain. Full-length keratin 16 cDNA sequence derived from the unaffected palm was completely normal, consistent with a postzygotic mutation as is suggested by the mosaicism observed. We defined this new clinical entity, "unilateral palmoplantar verrucous nevus", rather than localized or focal epidermolytic palmoplantar keratodermas, as the lesions are present only on one side of the body and follow Blaschko's lines. This study is a report of a mosaic mutation in keratin 16 and also the association of a mutation in the V1 domain of a type I keratin associated with a human disease.

Adolescent↗
PubMed2000

Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men.

AIMS: Serum C3 is a powerful indicator of the risk of myocardial infarction, which correlates with body mass index, serum lipids and blood pressure. This study was performed to ascertain whether such correlations may be explained by an association of C3 with fasting insulin, and to assess comparatively the relationships of C3 and traditional risk factors to previous myocardial infarction. METHODS AND RESULTS: The fasting levels of C3, insulin, and the main risk factors were evaluated in 1090 unselected men aged 55-64 years, including 129 cases of previous ischaemic events (51 myocardial infarctions). In multivariate analysis C3 was associated with insulin (r=0.27, P<0.0001), cholesterol (r=0.18, P<0.0001), body mass index (r=0.13, P<0.0001), glucose (r=0.12, P=0.0001), systolic blood pressure (r=0.10, P<0.001), triglycerides (r=0.09, P<0.01) and HDL-cholesterol (r=-0.06, P<0.05). These variables explained 31% of the total C3 variance. Alcohol consumption and physical activity correlated inversely with C3, while no correlation was found with smoking and family history of myocardial infarction. C3 was associated with previous myocardial infarction and stroke, but not with angina pectoris and peripheral arterial disease. In logistic regression the variables associated with previous myocardial infarction were C3 (P=0.011), family history of myocardial infarction (P=0.018), ex-smoker status (P=0.020), age (P=0.025), glucose (P=0.028) and HDL-cholesterol (P=0.051, inverse relationship). CONCLUSIONS: The association of C3 with myocardial infarction persists retrospectively, and is more significant than any other association of traditional risk factors with previous myocardial infarction. Of the many variables associated with C3, fasting insulin is its main covariate, which suggests that C3 is a marker of a pro-atherogenic metabolic imbalance partly coinciding with insulin resistance.

Biomarkers↗
PubMed2000

Quantitative nailfold capillary microscopy findings in patients with acrocyanosis compared with patients having systemic sclerosis and control subjects.

BACKGROUND: The morphologic capillary microscopy (capillaroscopy) pattern of acrocyanosis is characterized by hemorrhages, pericapillary edema, and widened capillaries. These findings can result in a difficult differential diagnosis with systemic sclerosis (SSc). OBJECTIVE: We sought to quantify the characteristics of the capillaroscopy pattern that distinguishes patients with acrocyanosis from patients with SSc and control subjects. METHODS: A videomicroscope with fiberoptic illumination and personal computer-based image processing was used to measure capillary density, giant capillaries, loop width, and arterial and venous limbs in 10 patients with acrocyanosis, 10 patients with SSc, and 10 healthy control subjects. RESULTS: Acrocyanotic patients differed in every quantitative parameter both from control subjects and patients with SSc. In particular, capillary density, which was reduced compared with that of control subjects, was much higher than that of patients with SSc: one giant capillary per finger was observed in 2 patients with acrocyanosis, whereas more than 2 giant capillaries per finger were observed in each patient with SSc. CONCLUSION: These differences may aid in making the distinction between the capillaroscopy patterns in acrocyanosis and SSc.

Adult↗
PubMed2000

Endothelial dysfunction in hypertension.

Endothelial cells release both relaxing and contracting factors that modulate vascular smooth muscle tone and also participate in the pathophysiology of essential hypertension. Endothelium-dependent vasodilation is regulated primarily by nitric oxide but also by an unidentified endothelium-derived hyperpolarizing factor and by prostacyclin. Endothelium-derived contracting factors include endothelin-1, vasoconscrictor prostanoids, angiotensin II and superoxide anions. Under physiological conditions, there is a balanced release of relaxing and contracting factors. The balance can be altered in cardiovascular diseases such as hypertension, atherosclerosis, diabetes and other conditions, thereby contributing to further progression of vascular and end-organ damage. In particular, endothelial dysfunction leading to decreased bioavailability of nitric oxide impairs endothelium-dependent vasodilation in patients with essential hypertension and may also be a determinant for the premature development of atherosclerosis. Different mechanisms of reduced nitric oxide activity have been shown both in hypertensive states and several cardiovascular diseases, and endothelial dysfunction is likely to occur prior to vascular dysfunction. Thus, the strategies currently used to improve endothelial dysfunction may result in decreased morbidity and mortality in hypertensive patients.

Angiotensin II↗
PubMed2000

Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.

Adolescent↗
PubMed2000

[Therapeutic strategies in the treatment of endothelial dysfunction: facts and outlook].

Endothelial cells play a key role in cardiovascular homeostasis by producing several vasoactive agents, which modulate basal vascular tone and structure. Traditional risk factors of atherosclerosis contribute to endothelial dysfunction through different mechanisms such as oxidative stress, modulation of constitutive nitric oxide synthase, activation of angiotensin-converting enzyme and presumably endothelin-1. The purpose of this review was to evaluate the results of experimental and human studies on several treatment options that could improve endothelial function. However, further studies are needed to evaluate whether these different classes of drugs may improve both vascular injury and cardiovascular morbidity and mortality.

Animals↗
PubMed2000

IFN-alpha and IL-18 exert opposite regulatory effects on the IL-12 receptor expression and IL-12-induced IFN-gamma production in mouse macrophages: novel pathways in the regulation of the inflammatory response of macrophages.

We characterized the IL-12 response of mouse macrophages in terms of modulation of IFN-gamma production by cytokines (IFN-alpha and IL-18) and regulation of IL-12 receptor expression. Beta1 and beta2 IL-12R chain mRNA expression increased with time in culture in the absence of exogenous stimulation, with concomitant acquisition of responsiveness to IL-12 for IFN-gamma production. Expression of the IL-12R beta1 chain mRNA was increased further following IL-12 treatment as a consequence of IFN-gamma expression. IL-12 response was regulated differentially by IFN-alpha and IL-18. Neutralization of endogenous type I IFN increased IFN-gamma secretion, whereas exogenous IFN-alpha reduced it. In contrast, IL-18 enhanced IFN-gamma mRNA accumulation and IFN-gamma secretion in IL-12-stimulated, but not -untreated, cultures. The opposite effects exerted by IFN-alpha and IL-18 mirror their mutual capacity of regulating-in a negative or positive manner, respectively-the expression of the IL-12R beta1 chain. We suggest that differential regulation of IL-12 response by IFN-alpha and IL-18 can represent previously unrecognized regulatory mechanisms for maintaining suitable levels of differentiation/activation in macrophages.

Animals↗
PubMed1999

The role of proopiomelanocortin-derived peptides in skin fibroblast and mast cell functions.

We have previously described proopiomelanocortin (POMC) gene-expression in human normal cultured dermal fibroblasts, and its dose- and time-dependent modulation by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). The aim of the work described here was to investigate POMC-derived peptide release in vitro by cultured fibroblasts following incubation with different concentrations of both TNF-alpha and TGF-beta for 24 hours (1, 5, and 10 ng/ml). The effect of simultaneous addition of both TNF-alpha and TGF-beta (10 ng/ml) was also evaluated. Culture supernatants of human skin fibroblasts were collected to detect adrenocorticotropin hormone (ACTH), alpha-melanotropin (alpha-MSH), and beta-endorphin (beta-EP) levels by specific immunoenzymatic assay. We investigated the in vitro histamine-releasing activity of the POMC-derived peptides, alpha-MSH and beta-EP, on human foreskin mast cells. Detection of cleavage products in supernatants from cultured normal human dermal fibroblasts indicated intracellular processing by POMC protein. We were able to measure detectable levels of all peptides in basal conditions. TNF-alpha addition resulted in an increase in beta-EP and ACTH levels. TGF-beta-stimulated fibroblasts showed no alteration in beta-EP and alpha-MSH levels, whereas ACTH release was significantly enhanced. Both alpha-MSH and beta-EP induced histamine release from human foreskin mast cells in vitro with beta-EP-induced histamine levels as high as those observed with the calcium ionophore, ionomycin. Our data document fibroblast POMC-derived peptide release and modulation by cytokines, suggesting that they have a possible role in extracellular matrix deposit regulation and skin inflammation.

Adrenocorticotropic Hormone↗
PubMed1999

Detection of clonal T-cell receptor gamma gene rearrangements in paraffin-embedded tissue by polymerase chain reaction and nonradioactive single-strand conformational polymorphism analysis.

The diagnosis of T-cell lymphoproliferative disorders, which frequently involve the skin and other extranodal sites, is often problematic because of the difficulty in establishing clonality in paraffin-embedded tissue. To this end, we developed a simple, nonradioactive method to detect T-cell receptor gamma (TCR-gamma) gene rearrangements by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) in paraffin-embedded tissue. Jurkat and HSB-2 cell lines and peripheral blood samples from normal individuals were used as monoclonal and polyclonal controls, respectively. DNA was extracted from 24 biopsies of T-cell lymphomas, 12 biopsies of reactive lymphoid infiltrates, and 2 biopsies of primary cutaneous large B-cell lymphomas. Vgamma1-8, Vgamma9, Vgamma10, Vgamma11, and Jgamma1/Jgamma2 consensus primers were used for TCR-gamma gene rearrangement amplification and PCR products were analyzed by nonradioactive SSCP. Monoclonal controls yielded a well-defined banded pattern, whereas all polyclonal T-cell controls showed a reproducible pattern of smears. We detected monoclonality in 20/21 (95%) T-cell lymphoma cases, whereas no dominant T-cell clones were found in any of the reactive lymphoid infiltrates or B-cell lymphomas. Sensitivity of 1-5% was demonstrated by serially diluting Jurkat cells in mononuclear blood cells from normal individuals. We conclude that nonradioactive PCR-SSCP for TCR-gamma gene rearrangement analysis is a useful adjunct to routine histological and immunophenotypic methods in the diagnosis of T-cell lymphoproliferative disorders in paraffin-embedded tissue.

Base Sequence↗
PubMed1999

Pigmented purpura-like eruption as cutaneous sign of mycosis fungoides with autoimmune purpura.

We describe the clinical and laboratory findings of a young man with mycosis fungoides. The disease was associated, since the early stages, with autoimmune purpura. Interferon alfa (IFN-alpha) administration improved this patient's condition, both the purpuric eruption and patchy cutaneous lesions, thus suggesting T-cell abnormalities may be responsible for the development of the disease.

Adolescent↗
PubMed1999

Expression of Bcl-2, p53, c-jun and c-fos protooncogenes in keloids and hypertrophic scars.

Keloids and hypertrophic scars represent a model of altered wound healing characterized by overproduction of extracellular matrix and dermal fibroblasts with high mitotic rate. Alteration of apoptosis and cell proliferation has been implicated in the etiology of keloids. The bcl-2 protooncogene encodes a protein that protects cells from programmed cell death while p53 protein functions as negative regulator of cell proliferation. Both protooncogenes have been shown to play a role in tissue homeostasis as apoptotic regulatory genes. The c-jun and c-fos protooncogenes are transactivating factors also involved in fibroblast proliferation. In our study we investigated, by immunohistochemistry, skin specimens from three clinically active hypertrophic scars and keloids, two resting keloids and two early phase morphea to detect both bcl-2 and p53 protein expression, in order to evaluate these apoptotic regulatory genes in different fibrotic conditions. The c-jun and c-fos, at protein and mRNA level, and Ki67 nuclear antigen expression were also investigated. In hypertrophic scars and active keloids we could detect intense Bcl-2 staining in basal keratinocytes and in scattered fibroblast-like and perivascular spindle-shaped cells, while no p53 expression could be demonstrated. The c-jun and c-fos mRNA and protein expression was mainly found in dermal fibroblast-like cells and elongated perivascular cells in all skin biopsies, and similar immunostaining pattern was observed for Ki67 antigen. No protooncogene expression in morphea patients and normal skin, unless Bcl-2 staining in the basal layer of normal epidermis, was documented. Our results suggest that Bcl-2, c-jun and c-fos protein expression and lack of p53 detection in fibroblast-like and perivascular spindle cells are related to increased fibroblast proliferation, confirmed by Ki67 positivity, probably due to alteration of these regulatory apoptotic genes resulting in pathological scarring.

Apoptosis↗