Biomedical subjects

C Caruso

Publications and source records attributed to C Caruso.

At least 37 records · Page 2Linked to original sources

PubMed2002

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population.

Classes I and II human leukocyte antigens (HLA) genes encode highly polymorphic heterodimeric glycoproteins involved in the control of immune responses. The HLA class I gene HFE seemingly no longer participates in immunity because it has lost its ability to bind peptides and it has acquired the ability to form complex with the receptor for iron-binding transferrin by regulating iron uptake by intestinal cells. Thus, it indirectly regulates immune responses too, because iron availability plays a role in specific and non-specific immune responses. The distribution of HFE polymorphisms in Sicilian centenarians and nonagenarians was studied to evaluate if HFE alleles might be represented differently in people selected for longevity. DNA samples were obtained from 106 young controls (age range from 22 to 55 years; 40 men and 66 women) and 35 elderly subjects (age range from 91 to 105 years; seven men and 28 women). Samples were typed for C282Y, H63D and S65C alleles using polymerase chain reaction and sequence specific primers. Among the young individuals, none was heterozygous for the C282Y or for S65C mutation. Twenty-six were heterozygous for H63D mutation. Among the elderly subjects, 11 were heterozygous for the C282Y mutation or for H63D mutation. None was heterozygous for the S65C mutation. No compound heterozygous individuals (C282Y/H63D) were found. A highly significant difference was observed in frequencies of C282Y alleles between the young and the elderly subjects on the whole. By analysing polymorphisms according to gender, heterozygous subjects for C282Y were found both in old men and in old women, but by comparing the allele frequencies to those of young people significance was attained only in women. Concerning H63D polymorphisms, no significant differences were observed, between old and young people, both in men and in women. Possession of C282Y allele, known to be associated with an increase of iron uptake, significantly increases women possibility to reach longevity. Thus, present data adds another piece of evidence to the complex puzzle of genetic and environmental factors involved in control of lifespan expectancy in humans.

Adult↗

PubMed2002

Gender-specific association between -1082 IL-10 promoter polymorphism and longevity.

Ageing is characterized by a pro-inflammatory status, which could contribute to the onset of major age-related diseases. Thus, genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. IL-10 is an appropriate candidate because it exerts powerful inhibitory effects on pro-inflammatory function. IL-10 production is controlled by several polymorphic elements in the 5' flanking region of IL-10 gene on 1q32 locus, involving alleles at two microsatellite regions and several polymorphisms in promoter region. We analysed in 190 Italian centenarians (>99 years old, 159 women and 31 men) and in 260 <60 years old control subjects (99 women and 161 men), matched for geographical distribution, genotype frequencies for -1082G-->A, -819C-->T and -592C-->A IL-10 proximal promoter gene biallelic polymorphisms by sequence specific probes. -1082G homozygous genotype was increased in centenarian men (P < 0.025) but not in centenarian women. No difference was found between centenarians and control subjects regarding the other two polymorphisms. The presence of -1082GG genotype, suggested to be associated with high IL-10 production, significantly increases the possibility to reach the extreme limit of human lifespan in men. Together with previous data on other polymorphic loci (Tyrosine Hydroxylase, mitochondrial DNA, IL-6, haemochromatosis, IFN-gamma), this finding points out that that gender is a major variable in the genetics of longevity, suggesting that men and women follow different strategies to reach longevity. Concerning the biological significance of this association, we have not searched for functional proves that IL-10 is involved. Thus, we should conclude that our data only suggest that a marker on 1q32 genomic region may be involved in successful ageing in man. However, recent data on IL-6 and IFN-gamma genes suggest that longevity is negatively associated with genotypes coding for a pro-inflammatory profile. Thus, it is intriguing that the possession of -1082G genotype, suggested to be associated with IL-10 high production, is significantly increased in centenarians.

Aged↗

PubMed2002

Genotype frequencies of the +874T-->A single nucleotide polymorphism in the first intron of the interferon-gamma gene in a sample of Sicilian patients affected by tuberculosis.

In the light of the key role played by interferon (IFN)-gamma in the control of tuberculosis, in the present paper we have evaluated the distribution of the functional +874T --> A IFN-gamma single nucleotide polymorphism (SNP) in Sicilian patients affected by tuberculosis. Our aim was to determine whether there is an association between the TT genotype, which has been suggested to be linked to an increased production of IFN-gamma, and resistance to chronic tuberculosis. DNA samples were obtained from 45 patients and 97 healthy controls. Polymorphism at +874 was identified using amplification refractory mutational system methodology. The +874T SNP was less frequent in patients than in controls (0.42 vs. 0.50) but the difference was not significant. The +874TT genotype, which has been suggested to be associated with high IFN-gamma production, was significantly decreased in the patients. Thus, resistance to chronic lung tuberculosis might be associated with a genetically determined high IFN-gamma production capacity. In conclusion, the present data add another piece of evidence to the complex puzzle of genetic and environmental factors involved in control of infectious diseases. Studies on cytokine gene polymorphisms may elucidate the complex network of trans-interactive genes influencing the type and strength of responses to environmental stressors and may help to identify the genetic factors that affect survival in humans.

Adult↗

PubMed2002

Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis.

BACKGROUND: Although anti-endomysial antibodies (EmA) have been found in the supernatants of cultured intestinal mucosa from patients with coeliac disease (CD), in no study has the clinical reliability of this new diagnostic tool been investigated. Our aims were to evaluate the clinical usefulness of the in vitro production of EmA in CD diagnosis in consecutive patients with suspected CD, and to evaluate the reliability of the in vitro challenge in CD patients on a gluten-free diet (GFD). METHODS: For the former aim, consecutive patients who were due to undergo intestinal biopsy for suspected diagnosis of CD were enrolled: according to the final diagnosis, these patients were divided into two groups: Group 1 comprised 91 newly diagnosed CD patients (40 males; age range 7 months to 84 years), Group 2 included 100 subjects with diseases other than CD (44 males; age range 9 months to 76 years). For the latter aim, we also studied 21 CD patients on a gluten-free diet after 16-123 months (8 males; age range 3-51 years), with normal intestinal architecture (Group 3) and 22 patients who served as controls (12 males; age range 4-60 years) with gastroesophageal reflux disease-like symptoms (Group 4). All patients underwent determination of serum anti-gliadin (AGA) and EmA antibodies, histology evaluation of the intestinal biopsies and EmA assay in the supernatants of in vitro gliadin-challenged duodenal mucosa. RESULTS: EmA assay in the supernatants showed a sensitivity and specificity of 96% and 100%, respectively; these were not significantly different from those observed for serum EmA (88% and 99%, respectively). However, EmA assay in the supernatants was useful in CD patients with mild intestinal histology lesions (infiltrative/hyperplastic type): in this subgroup it was positive in 9/12 of cases, but serum EmA was positive in only 2/12. As regards the reliability of the in vitro gliadin challenge, EmA production in supernatants was recorded only in 10/21 CD patients on a gluten-free diet. The patients with a positive in vitro challenge had a higher number of intra-epithelial lymphocytes than patients with a negative challenge. CONCLUSIONS: 1) EmA assay in the medium of cultured intestinal biopsy can detect gluten-sensitive enteropathy, characterized by an infiltrative/hyperplastic histological pattern, which is often associated with negative serum EmA. 2) The in vitro challenge in CD patients on a gluten-free diet detects EmA production in the culture medium only in half of the cases and other studies must be performed to evaluate whether EmA production after in vitro challenge can be considered a reliable test for confirming CD diagnosis.

Adolescent↗

PubMed2001

Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data.

Literature data suggest that human longevity may be directly correlated with optimal functioning of the immune system. Therefore, it is likely that one of the genetic determinants of longevity resides in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, studies performed on mice have suggested that the Major Histocompatibility Complex (MHC), known to control a variety of immune functions, is associated with the life span of the strains. In the last 25 years, a fair number of cross-sectional studies that searched for the role of HLA (the human MHC) genes on human longevity by comparing HLA antigen frequencies between groups of young and elderly persons have been published, but conflicting findings have been obtained. In fact, the same HLA antigens are increased in some studies, decreased in others and unchanged in others. On the whole, that could lead us to hypothesize that the observed age-related differences in the frequency of HLA antigens are due to bias. In our opinion, this hypothesis is real for most studies owing to major methodological problems. However, some studies that do not meet these biases have shown an association between longevity and some HLA-DR alleles or HLA-B8,DR3 haplotype, known to be involved in the antigen non-specific control of immune response. Thus, HLA studies in man may be interpreted to support suggestions derived from the studies on congenic mice on MHC effects on longevity. However, in mice the association may be by way of susceptibility to lymphomas whereas, in human beings, the effect on longevity is likely, via infectious disease susceptibility. Longevity is associated with positive or negative selection of alleles (or haplotypes) that respectively confer resistance or susceptibility to disease(s), via peptide presentation or via antigen non-specific control of the immune response.

Aging↗

PubMed2001

Recombinant wheat antifungal PR4 proteins expressed in Escherichia coli.

PR proteins are soluble and host-coded molecules with antifungal activity induced by a variety of agents. Wheat contains several PR proteins and among them are those of the class 4 coded wheatwin1 and wheatwin2; the two native proteins have been isolated from wheat kernel and the coding cDNA clones have been recently characterized. Herein, we report the expression of recombinant wheatwin1 and wheatwin2 in Escherichia coli-insoluble fractions; a new protocol for the purification in high yields and correct processing of the two proteins was developed. The recombinant proteins have molecular weights identical to that of the native proteins, indicating that the removal of the N-terminal methionine and cyclization of glutamine to pyroglutamate was complete. Both recombinant proteins inhibited in vitro the growth of Fusarium culmorum exhibiting antifungal properties similar to those of the native proteins.

Antifungal Agents↗

PubMed2001

A basic peroxidase from wheat kernel with antifungal activity.

A basic heme-peroxidase (WP1) was purified to homogeneity from wheat (Triticum aestivum) kernels. The protein was not glycosylated and exhibited a molecular mass of 36 kDa and a pI of 8.0. The N-terminal amino acid sequence revealed a very high similarity with a wheat flour peroxidase allergen associated with baker's asthma. WPI showed indole-3-acetic acid oxidase activity in the presence of Mn2+ and phenolic cofactors. Antifungal assays performed in vitro towards phytopathogenic fungi indicated that WP1 was active in inhibiting germ tube elongation. This first report on antifungal properties of a heme-peroxidase gives experimental support to the idea that peroxidases play a defensive role against invading pathogens.

Amino Acid Sequence↗

PubMed2001

A genetically determined high setting of TNF-alpha influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity.

The 8.1 ancestral haplotype (AH) is a common Caucasoid haplotype carried by most people who type for HLA-B8,DR3. It seems unique in its association with a wide range of immunopathologic diseases. Healthy subjects bearing this haplotype demonstrate several alterations of immune response. This article will focus on the identification of the mechanism(s) of disease susceptibility of 8.1 AH. In 13 carriers of 8.1 AH, and 43 negative patients, enzyme immune assays serum levels of tumor necrosis factor (TNF)-alpha, soluble endothelial leukocyte adhesion molecule-1 (sELAM-1), cortisol, and interleukin(IL)-10 were determined. In addition, quantification of cytokine produced in vitro after mitogen stimulation was studied, and all subjects were genotyped for alleles at -592, -819, and -1082 nucleotides of IL-10 gene 5' flanking region, which is known to control IL-10 production. Results revealed that 8.1 AH is associated with a high in vivo and in vitro production of TNF-alpha, which in turn seems responsible for increased serum levels of sELAM-1, cortisol, and IL-10. On the contrary, in vitro production of IL-10 is not increased in these patients and there are no differences in allele promoter frequencies between the two groups that might explain the differences in IL-10 serum values. Thus, serum values seem to be the result of the effects of increased serum levels of TNF-alpha and cortisol. In conclusion, the increased spontaneous release of TNF-alpha, which modifies a certain number of immunologic parameters, may be the most characterizing feature of 8.1 AH. The consequent modification of the immunologic scenario might be involved in the predisposition to the impressive number of diseases and the changes in immune response observed in the patients studied.

Adult↗

PubMed2001

Isolation and amino acid sequence of two new PR-4 proteins from wheat.

We have purified and characterized two new pathogenesis-related (PR) proteins from wheat belonging to the PR-4 family. We named the proteins wheatwin3 and wheatwin4 in analogy with the previously characterized wheatwin1 and wheatwin2. Their isoelectric points were 7.1 and 8.4, respectively. We determined the complete amino acid sequence of both proteins by a rapid approach based on the knowledge of the primary structures of the homologous wheatwin1 and wheatwin2. Wheatwin3 differs from wheatwin1 in one substitution at position 88, while wheatwin4 differs from wheatwin2 in one substitution at position 78. The secondary structure and solvent accessibility of these residues were determined on the three-dimensional model of wheatwinl. Residue 88 was very accessible and was located in a flexible region. Preliminary results indicate that, like wheatwin1 and wheatwin2, wheatwin3 and wheatwin4 have antifungal activity.

Alkylation↗

PubMed2001

Effects of in vitro treatment with fluticasone propionate on natural killer and lymphokine-induced killer activity in asthmatic and healthy individuals.

BACKGROUND: Topical corticosteroids are beneficial in the treatment of allergic respiratory disorders; they exert effects on a number of cells involved in allergic inflammatory reactions. On the other hand, major histocompatibility complex (MHC)-unrestricted cytotoxicity (i.e., natural killer [NK] cell activity) may play a role in the inflammatory allergic reaction. The objective was to gain insight into the mechanisms of the therapeutic effects of fluticasone propionate (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore, we evaluated the NK and lymphokine-activated killer (LAK) activity of effector cells in vitro treated or not with FP. METHODS: Evaluations were made on peripheral blood mononuclear cells (PBMNCs), obtained from healthy volunteers (n = 10) and from asthmatic atopic subjects (n = 10) with allergy to Parietaria. RESULTS: Asthmatic patients had significantly increased NK activity (P= 0.0008), and interleukin (IL)-2- (P=0.0005) and interferon (IFN)-alpha-induced LAK activities (P=0.0005). In both groups, FP 10(-7) M significantly reduced NK activity (P<0.0001), IL-2-induced LAK activity (P<0.0001), and IFN-alpha-induced LAK activity (P<0.0001). Similar results were obtained with FP 10(-8) M. CONCLUSIONS: Since MHC-unrestricted cytotoxicity has been implicated in the development of allergen-induced eosinophilic airway inflammation, inhibition of NK and LAK activity by FP may contribute to the steroid therapeutic effect in asthma.

Androstadienes↗

PubMed2001

Randomized double-blind study evaluating the efficacy on uterine fibroids shrinkage and on intra-operative blood loss of different length of leuprolide acetate depot treatment before myomectomy.

OBJECT: To determine whether length of pre-operative treatment with gonadotrophin-releasing hormone agonists (GnRHa) may have different effects on uterine shrinkage and intra-operative blood loss, 36 patients with symptomatic uterine fibroids awaiting myomectomy were randomly divided into two groups. METHOD: Twenty patients received long-term GnRHa administration, six monthly depot injections of leuprolide acetate (LA), while 16 patients were treated with two monthly LA injections before surgery. The hemoglobin concentration and estradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured before and after treatment in both groups. RESULTS: Uterine volume decreased in the long-term treated group from 680+/-276 cm3 to 486+/-195 cm3 (36%) after two and to 388+/-172 cm3 (51%) after six LA injections. In the short-term treated group the basal uterine volume decreased from 745+/-320 cm3 to 456+/-177 cm3 (39%) after two LA injections. The uterine volume decrease was statistically significant (p<0.05) after two LA injections in both groups while the decrease observed between two and six LA injections was not significant (p>0.05). The intra-operative blood-loss was not significantly different between the two groups studied, 315+/-93 cm3 and 336+/-88 cm3. CONCLUSION: Two pre-operative GnRHa depot injections offer similar results, in terms of uterine shrinkage and intra-operative blood loss, and a longer treatment seems to be justified in cases of anemia.

Adult↗

PubMed2001

Measurement of inflammatory mediators of mast cells and eosinophils in native nasal lavage fluid in nasal polyposis.

BACKGROUND: Nasal polyposis (NP) often coexists with asthma, rhinitis and sinusitis. Polyp histology typically shows chronic, eosinophilic inflammation. The inflammatory cell infiltrate generally includes eosinophils, lymphocytes, plasma cells and mast cells. OBJECTIVE: To gain insight into the natural history of NP, we analysed mediator levels and leukocyte values in nasal fluids and eosinophil cationic protein (ECP), total IgE levels and eosinophils in the blood in several groups of both allergic and non-allergic patients with nasal polyps and in patients with allergic rhinitis (AR). METHODS: Thirty-two patients with nasal polyps entered the study. As a control group, we studied 55 patients with AR, i.e. 20 patients with seasonal AR to grass pollen, 24 with AR sensitive to Parietaria and 11 with AR sensitive to house dust mite (HDM). Eighteen patients with nasal polyps were also allergic patients (8 were sensitive to Parietaria and 10 were sensitive to HDM), whereas 14 were non-allergic patients. Tryptase and histamine values were assayed in nasal fluids, whereas total IgE was determined in serum. ECP values were assayed both in nasal fluids and serum. Eosinophils were quantified both in the blood and nasal fluids. RESULTS: Tryptase levels were significantly higher in the nasal lavages from patients with NP than in those from patients without NP (4.7 vs. 3.5 U/l, p < 0.001) and correlated with symptom scores (r(s) = 0.42, p < 0.0001). The median levels of histamine in nasal fluids from patients with NP were also significantly higher than those observed in patients without NP (50.0 vs. 21.3 ng/ml, p < 0.001), but did not correlate with symptom scores. Finally, the median levels of ECP in nasal fluids from patients with NP were significantly higher than those observed in patients without NP (38.1 vs. 16.1 ng/ml, p < 0.001) and correlated with symptom scores (r(s) = 0.38, p < 0.001). Analysis of variance showed that, among the variables studied, the presence of nasal polyps was the factor responsible for the higher levels of tryptase, histamine and ECP in nasal fluids. With regard to leukocyte counts in nasal fluids, no significant differences were observed between rhinitis patients with NP and those without NP. With regard to serum ECP and serum total IgE, no significant differences were detected between the two groups under study. Blood eosinophil levels in patients with NP were significantly higher than those observed in patients without NP (5.8 vs. 5.6, p = 0.002). Analysis of variance showed that both the presence of nasal polyps and the type of sensitisation were important. Considering the total symptom scores, no significant differences were observed between rhinitis patients with NP and those without NP. CONCLUSIONS: The present findings are consistent with the view that chronic eosinophil mucosal inflammatory disease in NP involves a self-sustaining mechanism, i.e. local release of inflammatory mediators, independent of allergen stimulation of nasal mucosa. Increased release of inflammatory mediators contributes to the development of nasal polyps, determining oedema and an increased recruitment of inflammatory cells. Besides eosinophils, mast cells also play a key role in this process.

Adolescent↗

PubMed2000

Early activation of gammadelta T lymphocytes in the elderly.

T cell function is altered in vivo and in vitro in elderly compared with young subjects, and this alteration is believed to contribute to morbidity and mortality in man due to the greater incidence of infection, as well as autoimmunity and cancer in elderly. The majority of T cells express TCRalphabeta whereas TCRgammadelta is expressed on a minority of T cells. Moreover, it is known that gammadelta T lymphocytes display major histocompatibility complex (MHC)- unrestricted cytotoxicity that is reminiscent of natural killer (NK) activity. In view of earlier findings on both T cells and NK cells in the elderly, we hypothesised a different behaviour of gammadelta T lymphocytes from old subjects when compared with gammadelta T lymphocytes obtained from young people. Therefore, to gain further insight into mechanisms of immunosenescence in this little-studied population, we studied immunofluorescence analysis gammadelta T cells from the elderly. Our preliminary results show that the percentage of blood gammadelta T cells in lymphocytes from old subjects is decreased when compared with the young. Interestingly, these cells are more activated in the elderly than in young subjects; expression of CD69, an early activation marker, is increased in gammadelta T lymphocytes from old subjects after three hours of in vitro culture both with and without lipopolysaccharide stimulation. Thus, our findings, which need confirmation, strongly suggest that, in humans, gammadelta T cells are early responders when compared with alphabeta T cells. They may act as 'first aid' cells to replace the described deficit of the specific and aspecific immunity in elderly. In this view, the proinflammatory status, observable in the elderly, renders them ready to be stimulated by exogenous agents.

Adult↗

PubMed2000

HLA, aging, and longevity: a critical reappraisal.

Despite a large number of studies, available data do not allow at present to reach definitive and clear conclusions on role of HLA on longevity, owing to major methodological problems, such as serological and molecular typing of different loci, insufficient sample sizes, different inclusion criteria and age cut-off, inappropriate mixing of data referred to people from 58 to over 100 years of age, inappropriate control matching, and neglected consideration of sex-related effects and the different genetic make-up of studied populations. However, within this confused scenario, some data emerge. First, two studies that do not fit the biases above discussed show that some HLA alleles are associated with longevity. However, some of these alleles may confer an increased risk to undergo a variety of diseases. Second, longevity may be associated with an increased homozygosity at HLA loci. Third, an intriguing association between longevity and the 8.1 ancestral haplotype (AH), which has been proven to be associated with a variety of immune dysfunctions and autoimmune diseases, apparently emerges. This association appears to be a sex-specific (males) longevity contributor, and it is particularly interesting, taking into account that a type 2 (early infancy) --> type 1 (adulthood) --> type 2 (aging) shift of cytokine profile occurs lifelong, and that individuals bearing this haplotype show a type 2 immune responsiveness (note that type 1 cytokines mainly enhance cellular responses, whereas type 2 cytokines predominantly enhance humoral responses). On the whole, the (sex specific) association of longevity with alleles or haplotypes of several genes related to risk factors for a variety of diseases (cardiovascular diseases, cancer), including HLA alleles and haplotypes, is not unexpected on the basis of previous studies on the genetics of longevity in centenarians. This association can be interpreted under the perspective of a well known evolutionary theory of aging (antagonistic pleiotropy). This theory predicts that the same gene (or allele or haplotype) can have different roles (positive or negative) in different periods of the life span. Thus, the 8.1 AH should exert a positive effect during the infancy and aging but not in adulthood, when, indeed it is associated to susceptibility to a variety of diseases.

Aged↗

PubMed2000

In vitro treatment with interleukin-2 normalizes type-1 cytokine production by lymphocytes from elderly.

The term immunosenescence is taken to mean the deterioration of immune function seen in elderly, which is manifested in increased susceptibility to infectious diseases, neoplasias, and autoimmune diseases. It is only recently that we have begun to understand the cellular and molecular changes involved. Of special interest in this regard are observations of a decline in synthesis of Type-1 cytokines which predisposes to diminished cell mediated immunity. We have evaluated the production of type 1 cytokines in old and young donors either in presence or in absence of recombinant interleukin-2 (rIL-2). Lymphocytes were stimulated with plastic bound anti-CD3 and after 48 h the supernatants were harvested and stored at -70 degrees C until assay. Type 1 cytokine, i.e. IL-12 and interferon-gamma (IFN-gamma) production by anti-CD3 stimulated lymphocytes from old subjects was significantly reduced when compared to that from young ones. This impaired production was reversed by adding rIL-2 in the culture medium. In previous studies on aged subjects, we have been able to demonstrate that in vitro treatment with rIL-2 completely restores proliferative responses and partially rescues the increased apoptosis of T cell cultures. Present and previous results suggest that rIL-2 completely restores Type 1 responses by overcoming the well known costimulation deficit of aged lymphocytes.

Adult↗

PubMed1999

Probing the modelled structure of wheatwin1 by controlled proteolysis and sequence analysis of unfractionated digestion mixtures.

We set up a method to get rapid information on the three-dimensional structure of peptide and proteins of known sequence. Both native and alkylated polypeptide is hydrolyzed with a number of proteases at different digestion times and the resulting mixtures are compared by HPLC analysis to establish the differences in the hydrolysis pathways of the folded and unfolded molecule. Then, the unfractionated digestion mixtures of the native polypeptide are submitted to automatic sequence analysis to identify the hydrolysis sites. The sequence of each fragment present in the mixtures is reconstructed and its amount determined by quantitative data of the sequence analyses. We used this approach to determine the amino acid surface accessibility of wheatwin1, a pathogenesis-related protein from wheat, and constructed a predictive three-dimensional model based on the knowledge of the tertiary structure of barwin, a highly homologous protein from barley. The procedure allowed us to quickly identify and quantify the hydrolysis at the susceptible bonds which could be classified as exposed, partially hidden, or inaccessible. The results were useful to evidentiate and discuss concordances and differences between experimental and model predicted accessibilities of amino acid residues. Proteins 1999;36:192-204.

Alkylation↗

PubMed1999

Granulocyte and natural killer activity in the elderly.

The deterioration of the immune system in ageing, 'immunosenescence', is thought to contribute to increased morbidity and mortality from infections and possibly autoimmune diseases and cancer. The most profound changes involve effector and immunoregulatory T-cell functions. Immunosenescence appears also to be related to changes in non specific immunity as well. In the present study we have assessed superoxide production, chemotaxis and the expression of the apoptosis-related molecule APO1/Fas (CD95) on neutrophils (PMN) from young and old subjects. Furthermore, we have measured the basal natural killer (NK) activity of young and elderly subjects and we have compared the number of CD16+ cells found in these two groups. We observed a significant decrease age-related both of formation of O2- and chemotaxis whereas no significant correlation between age and the expression of CD95 on granulocyte membrane was demonstrated, suggesting that an increase age-related of CD95-linked apoptosis of PMN should be not an important determinant in the decreased PMN function. We also observed a significant correlation between age and NK activity. The decreased NK cell function was not due to a decreased number of NK cells in effector cell preparations since the number of CD16+ cells was significantly increased in old subjects. In conclusion, our results show that in the elderly there is also a deficit of the aspecific immunity that might play a role in the pathogenic mechanisms of the immunosenescence.

Adult↗

PubMed1999

T cells and aging (update february 1999).

Deterioration of the immune system with aging ("immunosenescence") is believed to contribute to morbidity and mortality in man due to the greater incidence of infection, as well as possibly autoimmune phenomena and cancer in the aged. Dysregulation of T cell function is thought to play a critical part in these processes. Factors contributing to T cell immunosenescence may include a) stem cell defects, b) thymus involution, c) defects in antigen presenting cells (APC), d) aging of resting immune cells, e) disrupted activation pathways in immune cells, f) replicative senescence of clonally expanding cells. This review aims to consider the current state of knowledge on the scientific basis for and potential clinical relevance of those factors in immunosenescence.

Aging↗