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P Castiglioni

Publications and source records attributed to P Castiglioni.

At least 19 recordsLinked to original sources
PubMed2006

Diastolic dysfunction in human cardiac allografts is related with reduced SERCA2a gene expression.

Previous studies demonstrated that impaired left ventricular (LV) relaxation in cardiac allografts limits exercise tolerance post-transplant despite preserved systolic ejection fraction (EF). This study tested in human cardiac allografts whether the isovolumic relaxation time (IVRT), which provides the basis for most of diastolic LV filling, relates with gene expression of regulatory proteins of calcium homeostasis or cardiac matrix proteins. Gene expression was studied in 31 heart transplant recipients (25 male, 6 female) 13-83 months post-transplant with LVEF >50%, LV end-diastolic pressure <20 mmHg, normal LV mass index and without allograft rejection or significant cardiac pathology. IVRT related with the other diastolic parameters e-wave velocity (r = -0.46; p = 0.01), e/a-wave ratio (r = -0.5; p < 0.01) but not with heart frequency (r = -0.16; p = 0.4). No relation of IVRT was observed for immunosuppression, mean rejection grade or other medication. IVRT was not related with gene expression of desmin, collagen I, phospholamban, the Na+-Ca2+ exchanger, the ryanodine receptor or interstitial fibrosis but correlated inversely with SERCA2a (r = -0.48; p = 0.02). Prolonged IVRT is associated with decreased SERCA2a expression in cardiac allografts without significant other pathology. Similar observations in non-transplanted patients with diastolic failure suggest that decreased SERCA2a expression is an important common pathomechanism.

Adult↗
PubMed2006

Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP.

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5+/-2.4 to 7.5+/-2.9 ms x mmHg(-1)), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index. The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.

Adult↗
PubMed2004

Spontaneous transgenesis of human B lymphocytes.

DNA can cross the cell membrane by natural means, but the functional relevance of this phenomenon has not been fully elucidated. Here, we analyzed spontaneous transgenesis of human B cells using plasmid DNA coding for a functional immunoglobulin (Ig) heavy chain gene under the control of a B-cell-specific promoter. Using polymerase chain reaction (PCR), reverse transcriptase-PCR, and flow cytometry in combination, spontaneous transgenesis was documented in Burkitt's lymphoma cell lines, Epstein-Barr virus-transformed cell lines, and peripheral blood B lymphocytes of the mature naïve phenotype (IgM(+)/IgD(+)/CD27(-)). By immunoelectron microscopy, the internalized DNA was seen in the lysosomes/late endosomes and in the cytosol proximal to the nucleus. Importantly, spontaneously transgenic B cells processed and presented to major histocompatibility complex (MHC)-restricted T lymphocytes a peptide expressed in the transgenic product. This is the first demonstration that primary B lymphocytes possess a program for the spontaneous internalization of DNA, which in turn imparts the cell with new immunological functions. As spontaneous transgenesis is obtained using a nonviral vector, does not require prior cell activation, and is not associated with chromosomal integration, the findings reported here open new possibilities for genetic manipulations of mature naïve B lymphocytes for therapy and vaccination.

B-Lymphocytes↗
PubMed2003

Multi- and monofractal indices of short-term heart rate variability.

Indices of heart rate variability (HRV) based on fractal signal models have recently been shown to possess value as predictors of mortality in specific patient populations. To develop more powerful clinical indices of HRV based on a fractal signal model, the study investigated two HRV indices based on a monofractal signal model called fractional Brownian motion and an index based on a multifractal signal model called multifractional Brownian motion. The performance of the indices was compared with an HRV index in common clinical use. To compare the indices, 18 normal subjects were subjected to postural changes, and the indices were compared on their ability to respond to the resulting autonomic events in HRV recordings. The magnitude of the response to postural change (normalised by the measurement variability) was assessed by analysis of variance and multiple comparison testing. Four HRV indices were investigated for this study: the standard deviation of all normal R-R intervals; an HRV index commonly used in the clinic; detrended fluctuation analysis, an HRV index found to be the most powerful predictor of mortality in a study of patients with depressed left ventricular function; an HRV index developed using the maximum likelihood estimation (MLE) technique for a monofractal signal model; and an HRV index developed for the analysis of multifractional Brownian motion signals. The HRV index based on the MLE technique was found to respond most strongly to the induced postural changes (95% CI). The magnitude of its response (normalised by the measurement variability) was at least 25% greater than any of the other indices tested.

Electrocardiography↗
PubMed2002

Cross-priming is under control of the relB gene.

Cross-priming is an important mechanism of intercell transfer of antigenic material leading to the specific activation of cytotoxic T lymphocytes. Dendritic cells (DCs) are considered the central antigen-presenting cell in cross-priming. Here we decided to probe the role of the relB gene, a regulator of DC differentiation, in the in vivo cross-priming of a model tumour antigen, TAP(-/-) murine embryo cells (MEC), expressing human adenovirus type 5 early region 1. To this end, we used relB(-/-) mutant mice to generate bone marrow (BM) chimeras as these possess few residual DC but are capable of initiating CD4+ and CD8+ T-cell responses in vivo. Our results show that relB(-/-) BM chimeras are unable to cross-prime CD8+ T cells, suggesting that the relB gene regulates cross-priming.

Animals↗
PubMed2001

Time versus frequency domain techniques for assessing baroreflex sensitivity.

BACKGROUND: Newer techniques to evaluate baroreflex sensitivity (BRS) are based on the analysis of blood pressure (BP) and heart rate (HR) time series in the time or frequency domain. These novel approaches are steadily gaining popularity, since they do not require injection of vasoactive substances, nor do they rely on a complex experimental set-up. AIM: This review outlines and compares some basic features of the latest methods to assess spontaneous baroreflex function. RESULTS: Modern techniques for the estimation of spontaneous BRS are based on a variety of signal processing schemes and derive information on the baroreflex function from different perspectives. Thus factors such as respiration and other non-stationary agents may have different influences on the estimates provided by each of these approaches. Notwithstanding such individual specificity, however, it has been observed that in several physiological and pathophysiological conditions these techniques often provide comparable information on BRS changes over time, particularly when the estimates are averaged over time windows of a few minutes. CONCLUSIONS: Due to the general agreement in the pattern of BRS among most modern methods, it seems reasonable to employ the most validated of these techniques, for which data obtained in several studies are already available.

Animals↗
PubMed2001

Blood pressure and heart rate variability and baroreflex sensitivity before and after brain death.

OBJECTIVES: To evaluate spontaneous blood pressure and heart rate variability and spontaneous baroreflex sensitivity before and after brain death. METHODS: Spontaneous variability of arterial blood pressure and heart rate-estimated by power spectra of systolic (SBP) and diastolic blood pressure (DBP) and pulse interval (PI)-and spontaneous baroreflex sensitivity (BRS)-estimated by the alpha index and the sequence technique-were evaluated in 11 patients twice: shortly before and 1 hour after the onset of brain death. RESULTS: Significant spectral changes occurred after brain death: a general power reduction in PI spectra; a shift of SBP, DBP and PI powers toward the lower frequencies, resulting in a greater slope of the "1/f" spectral trends; and a marked reduction of SBP and DBP powers (-93%) and of SBP-PI coherence (-63%) at 0.1 Hz. The estimated average BRS was relatively high before brain death (around 11 ms/mm Hg), and fell close to 0 or even was not detectable at all after brain death. CONCLUSIONS: Parameters describing spontaneous blood pressure and heart rate variability and indexes reflecting the baroreflex function, which were relatively normal up to a few hours before brain death, underwent marked changes with the onset of brain death. All the changes found are likely to reflect the cessation of activity of the cardiovascular brain stem centres. These findings indicate that techniques of blood pressure and heart rate spectral analysis and of dynamic assessment of baroreflex sensitivity may be useful to complement the diagnosis of brain stem death.

Adult↗
PubMed2001

Baroreflex effectiveness index: an additional measure of baroreflex control of heart rate in daily life.

In healthy subjects, progressive beat-to-beat increases or decreases in systolic blood pressure (SBP) ramps are not always accompanied by baroreflex-driven lengthening or shortening in pulse interval (PI) ramps, respectively. This phenomenon has been quantified by a new index, the baroreflex effectiveness index (BEI), defined as the ratio between the number of SBP ramps followed by the respective reflex PI ramps and the total number of SBP ramps observed in a given time window. Specificity of BEI was shown in eight cats by a -89% reduction of BEI after sinoaortic denervation. In 14 healthy humans, the 24-h average BEI value was 0.21, with a marked day-night modulation ( approximately 0.25 day, approximately 0.15 night) in counterphase with modulation of baroreflex sensitivity (BRS). Our analysis indicates that 1) in normal subjects, arterial baroreflex can induce beat-by-beat PI changes in response to only 21% of all SBP ramps, possibly because of central inhibitory influences or of interferences at sinus node level by nonbaroreflex mechanisms and 2) BEI provides information on the baroreflex function that is complementary to BRS.

Adult↗
PubMed2001

[Blood pressure variability].

This review deals with a number of issues related to blood pressure variability. These include: historical aspects, with reference to the first pioneering observations; methodological aspects, focusing on the different methods for quantifying blood pressure variability; description of the characteristics of blood pressure variability over the 24 hours; mechanisms involved in determining the different magnitude of this phenomenon in different subjects, such as behavioral factors, central and reflex neural influences, humoral and mechanical factors; blood pressure variability as a probe to assess spontaneous baroreflex sensitivity; effects of aging and hypertension on blood pressure variability, with a discussion of the clinical relevance of this phenomenon in the prognostic evaluation of patients; effects of drugs on blood pressure variability. Finally methodological aspects related to the use of noninvasive ambulatory blood pressure monitoring in the assessment of blood pressure variability are discussed.

Aging↗
PubMed2000

Relevance of the tumor antigen in the validation of three vaccination strategies for melanoma.

Many preclinical studies of cancer immunotherapy are based on the testing of a single vaccination strategy in several tumor models. Moreover, most of those studies used xenogeneic Ags, which, owing to their high immunogenicity, may not represent realistic models for the validation of cancer immunotherapies. To address these issues, we compared the vaccination efficacy of three well established strategies (i.e., naked DNA; peptide-pulsed dendritic cells (DC), or a mixture of peptide and the Escherichia coli toxin LTR72) using the xenogeneic OVA or the naturally expressed tyrosinase-related protein 2 (TRP-2) tumor Ag in the B16 melanoma model. C57BL/6 mice received one to three s.c. injections of peptide-pulsed DC or DNA, or one to four mucosal administrations of peptide-toxin mixture. One to 2 wk later, the animals were challenged s.c. with B16 or B16 cells expressing OVA (B16-OVA). Vaccination of mice with OVA induced in all cases melanoma-specific CTL and protection against B16-OVA. When TRP-2 was used, all three vaccines elicited B16-specific CTL, but only DC pulsed with the immunodominant T cell epitope TRP-2181-188 allowed protection against B16. Even more importantly, a vaccination regimen with TRP-2-pulsed DC, started 24 h after the injection of a lethal number of B16 cells, caused a therapeutic effect in 60% of the challenged animals. Our results strongly emphasize the relevance of the tumor Ag in the definition of immunotherapeutic strategies for cancer, and support the use of peptide-pulsed DC as cancer vaccine in humans.

Administration, Intranasal↗
PubMed2000

Genetics of mutations affecting the development of a barley floral bract.

Two groups of mutants that affect the morphology of the lemma, a floral bract of barley, are described. The first comprises phenotypes associated with mutant alleles of calcaroides loci. On the lemma of these mutants, a well-organized neomorphic structure is formed, termed the sac. We provide a morphological description of wild-type (WT) and mutant lemmas, based on scanning electron microscopy (SEM), showing that both consist of similar tissues, but that the mutant is characterized by reversed growth polarity. The sac is a unique structure among grasses, and it is remarkable that recessive mutations at five different genetic loci lead to the same organ. The second group of mutants carry recessive alleles of two leafy lemma genes, both of which are necessary to cause the transformation of the lemma into a structure having all characteristics of a vegetative leaf, as shown by SEM analysis. The presence of sheath, blade, and ligule in the mutant lemma suggests that wild-type lemma development is interrupted at a leaf-like stage. The genes cal a, b, C, d, 23, lel1, and lel2 have now been mapped at precise positions on linkage groups 2, 7, 7, 3, 7, 5, and 7, respectively. The mutants considered in this article are unaffected in other floral organs. A model for lemma development is suggested.

Hordeum↗
PubMed2000

Lacidipine and blood pressure variability in diabetic hypertensive patients.

The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power approximately 0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P<0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (-19.6%, -14.4%, and -24.0%, respectively; P<0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7+/-1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7+/-1.8 ms/mm Hg, P<0.01), with a significant increase being obtained also for the 24-hour average alpha coefficient at 0.1 Hz (from 5.7+/-1.5 to 6.4+/-1.3 ms/mm Hg, P<0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.

Antihypertensive Agents↗
PubMed1999

Effect of sinoaortic denervation on frequency-domain estimates of baroreflex sensitivity in conscious cats.

In animals and humans, baroreceptor modulation of the sinus node in daily life can be studied by identification of the number of sequences in which systolic blood pressure (SBP) and pulse interval (PI) linearly decrease or increase for several beats. It is also studied by power spectral analysis of SBP and PI in regions where their powers are coherent, although, in contrast to the sequence method, whether this frequency-domain method specifically reflects the baroreceptor-heart rate reflex has not been adequately tested. We recorded intra-arterial BP for approximately 3.5 h in eight conscious cats, first intact and then 7-10 days after sinoaortic denervation (SAD). Sensitivity of baroreceptor-heart rate reflex was assessed in 120-s segments by the square root of the ratio of PI and SBP spectral powers (alpha) in the regions around 0.1 (MF) and 0.3 (HF) Hz, and coherence between PI and SBP spectral powers in MF and HF regions was computed. SAD increased overall SBP variability and reduced PI variability throughout the frequency range examined. SAD markedly reduced (P < 0.01) both alpha-MF (-65.6%) and alpha-HF (-79. 9%) and consistently reduced the number of coherent segments [i.e., where coherence (K2) > 0.5] and average coherence values in the MF region. In the HF region, however, SAD did not alter the number of coherent segments, and although average coherence value throughout the HF band was reduced, in restricted portions of the band (different between animals), a high coherence value survived denervation. No significant changes were seen in any measured variables in five sham-operated cats. Thus the frequency-domain method specifically reflects baroreflex modulation of heart rate in the MF region only. In the HF region, in contrast, baroreflex and nonbaroreflex influences on the sinus node both contribute to a variable degree to determination of heart rate responses to BP oscillations. If used to study baroreflex function in daily life, this method should use the coefficient derived from MF data.

Animals↗
PubMed1999

Broad-band spectral analysis of 24 h continuous finger blood pressure: comparison with intra-arterial recordings.

The present study compares the spectral characteristics of 24-h blood pressure variability estimated invasively at the brachial artery level with those estimated by measurement of blood pressure at the finger artery using the non-invasive Portapres device. Broad-band spectra (from 3x10(-5) to 0.5 Hz) were derived from both finger and intra-brachial pressures recorded simultaneously for 24 h in eight normotensive and twelve hypertensive ambulant subjects. At frequencies lower than 0.07 Hz, higher spectral estimates were obtained by Portapres than by intra-brachial measurements. The maximum overestimation occurred in systolic pressure at around 10(-2) Hz, where the amplitude of the oscillations was two times greater when measured by Portapres. A less pronounced overestimation was found for diastolic pressures. The maximum overestimation was greater during daytime than during night-time. At around 0.1 Hz, invasive and non-invasive spectra were similar. At the respiratory frequencies (0.15-0.50 Hz), the power spectra were overestimated by Portapres during daytime, and underestimated at night. These results provide reference information for the correct interpretation of Portapres data in the estimation of 24-h blood pressure spectral power.

Adult↗
PubMed1998

An AFLP-based procedure for the efficient mapping of mutations and DNA probes in barley.

A strategy based upon AFLP markers for high-efficiency mapping of morphological mutations and DNA probes to linkage groups in barley is presented. First, 511 AFLP markers were placed on the linkage map derived from the cross Proctor x Nudinka. Second, loci controlling phenotypic traits were assigned to linkage groups by AFLP analysis, using F2 populations consisting of 30-50 mutant plants derived from crosses of the type "mutant x Proctor" and "mutant x Nudinka." To map DNA probes, 67 different wild-type barley lines were selected to generate F2 populations by crossing with Proctor and Nudinka. F2 plants that were polymorphic for a given RFLP fragment were classified into genotypic classes. Linkage of the RFLP polymorphism to 1 of the 511 AFLP loci was indicated by cosegregation. The use of the strategy is exemplified by the mapping of the mutation branched-5 to chromosome 2 and of the DNA probes Bkn2 and BM-7 to chromosomes 5 and 1, respectively. Map expansion and marker order in map regions with dense clustering of markers represented a particular problem. A discussion considering the effect of noncanonical recombinant products on these two parameters is provided.

Alleles↗