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Biomedical subjects

P Castiglioni

Publications and source records attributed to P Castiglioni.

At least 19 recordsLinked to original sources
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↗
PubMed1998

Estimation of blood pressure variability from 24-hour ambulatory finger blood pressure.

Portapres is a noninvasive, beat-to-beat finger blood pressure (BP) monitor that has been shown to accurately estimate 24-hour intra-arterial BP at normal and high BPs. However, no information is available on the ability of this device to accurately track ambulatory BP variability. In 20 ambulatory normotensive and hypertensive subjects, we measured 24-hour BP by Portapres and through a brachial artery catheter. BP and pulse interval variabilities were quantified by (1) the SDs of the mean values (overall variability) and (2) spectral power, computed either by fast Fourier transform and autoregressive modeling of segments of 120-second duration for spectral components from 0.025 to 0.50 Hz or in a very low frequency range (between 0.00003 and 0.01 Hz) by broadband spectral analysis. The 24-hour SD of systolic BP obtained from Portapres (24+/-2 mm Hg) was greater than that obtained intra-arterially (17+/-1 mm Hg, P<0.01), but the overestimation was less evident for diastolic (3+/-1 mm Hg, P<0.01) and mean (3+/-1 mm Hg, P<0.01) BP. The BP spectral power <0.15 Hz was also overestimated by Portapres more for systolic than for diastolic and mean BPs; similar findings were obtained by the fast Fourier transform, the autoregressive approach, and focusing on the broadband spectral analysis. BP spectral power >0.15 Hz obtained by the Portapres was similar during the day but lower during the night when compared with those obtained by intra-arterial recordings (P<0.01). No differences were observed between Portapres and intra-arterial recordings for any estimation of pulse interval variabilities. The overestimation of BP variability by Portapres remained constant over virtually the entire 24-hour recording period. Thus, although clinical studies are still needed to demonstrate the clinical relevance of finger BP variability, our study shows that Portapres can be used with little error to estimate 24-hour BP variabilities if diastolic and mean BPs are used. For systolic BP, the greater error can be minimized by using correction factors.

Adult↗
PubMed1997

Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus.

Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age +/- SD 41.9 +/- 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (-71.3% and -60.2% respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (-57.0% and -43.5%, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i.e. under conditions suitable for routine outpatient evaluation.

Adult↗
PubMed1997

Dynamic detection of rhythmic oscillations in heart-rate tracings: a state-space approach based on fourth-order cumulants.

This paper presents a new procedure specifically aimed at providing a dynamical detection of the oscillations occurring in long-term heart-rate (HR) tracings. The procedure is based on a time-variant state-space modelling of the fourth-order cumulants of the HR signal. The state-space estimator was selected because of its demonstrated capability to distinguish between deterministic and stochastic components of the signal, while the fourth-order cumulants of the signal were used as input of the model to further reduce adverse effects of coloured, white and l/f Gaussian noise possibly present in the input data. The procedure was tested by the analysis of simulated signals and its performance was compared with the results obtained by state-space modelling applied directly on the test signals (instead of on the fourth-order cumulants of the signals) and by the more traditional auto-regressive modelling. The comparison has shown a clear superiority of the proposed procedure over the other techniques in discriminating deterministic oscillations from coloured noise. Finally, the applicability of the procedure to biological data was verified by analysing five experimental HR tracings recorded in normal subjects during laboratory and daily life conditions.

Electrocardiography↗
PubMed1997

Dap (Defective aleurone pigmentation) mutations affect maize aleurone development.

Dap (Defective aleurone pigmentation) is the designation for mutations in maize that give rise to a characteristic dappled endosperm phenotype, consisting of patches of purple tissue, of variable size and shape, on a yellow background. Features shared by all Dap mutants are: dominant expression when they are maternally derived, lack of expression or transmission when they originate from pollen, failure to recover homozygous Dap genotypes, reduced frequency of Dap seeds in the progeny of outcrosses of Dap/+ females, association of the dappled phenotype with reduction in seed size. The mutants so far tested, six in all, can be grouped into two classes, one including male-transmissible (MT) isolates not expressed in the endosperm if their contribution is paternal, and a second class of isolates (NMT) that are permanently lost following paternal transmission. We suggest that the NMT mutations are on a chromosome that carries an intercalary deletion. Assuming linkage between the mutant and the deletion, selection against the deficient chromosome during male gametogenesis would account for the failure to recover Dap seeds in the progeny of Dap/+ male parents. We have obtained genetic evidence supporting this hypothesis. This interpretation, however, does not apply to MT alleles. For these, other mechanisms, such as imprinting and/or dosage effects may be proposed. The mutable pattern in the endosperm to which all Dap mutants give rise is an intriguing phenotype which remains to be clarified. An unexpected finding is that aleuronic and subaleuronic cells corresponding to the colourless areas are abnormal in shape and anthocyanin biosynthesis is blocked in these cells. This finding calls for further investigation in light of a possible connection between flavonoid precursors and cell shape.

Anthocyanins↗