The impairment of phytohaemagglutinin-triggered lymphocyte proliferation represents a prominent immunologic abnormality in elderly individuals. To assess whether the reduced function is related to a ...CD28/B7 signalling deficiency, purified T lymphocytes and antigen presenting cells (APCs) were analyzed for their phenotypic profile and/or functional capacities. T cell responses to immobilized OKT3 monoclonal antibodies (mAb) or a combination of anti-CD2 mAb and phorbol esters were unaffected in old subjects when compared to the younger counterpart. In contrast, CD28 costimulation in the presence of OKT3 or anti-CD2 mAb, gave rise to significantly diminished T cell proliferative responses. These findings correlated with a marked decline of CD28
+ T cell frequency, which mainly involved the CD4
−CD45RO
− cell subset. The defect in CD28 expression could not be reversed by T cell stimulation, as a comparable increase in CD28 levels occurred in both `aged' and `young' T cells after in vitro activation. Moreover, the elderly group did not exhibit a reduction of interleukin (IL)-2 synthesis, as assessed at 24 h of culture, regardless of the stimulant used. Finally, B7.2 (CD86) expression by `aged' CD14
+ APCs was unaffected in both resting and interferon-
γ activated cells. These results suggest that an intrinsic defect in CD28 expression might in part account for the age-related decline of T cell proliferative responses.
Abstract
The release of soluble circulating molecules represents a prominent feature during the course of immune-mediated clinical conditions. To further assess the relationship between serum ...concentrations of adhesion or apoptotic-related soluble structures and liver diseases, we evaluated the levels of intercellular adhesion molecule-1 (sICAM-1), Fas receptor (CD95) and Fas ligand (sCD95L) in a group of patients affected by Hepatitis C Virus (HCV)induced chronic hepatitis (CH-C), HCV-positive liver cirrhosis with superimposed hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and alcoholic liver cirrhosis (ALC). Results show that sICAM-1 values were in all instances significantly elevated when compared to those seen in healthy donors. Similar findings were noted in subjects with liver diseases in terms of sCD95 concentrations, even if to a different degree of statistical significance. Finally, sCD95L amounts were augmented in AIH, PBC, ALC and CH-C in comparison to controls, while in the HCC counterpart sCD95L levels fell within normal range.
All together, these findings emphasize the occurrence of circulating soluble molecules in patients with various chronic liver diseases, likely reflecting the involvement of several pathogenetic mechanisms.
The epidemiological associations of gallstone disease were evaluated in a population of 2,325 civil servants (1,244 men and 1,081 women) in Rome, Italy, which was enrolled in a cross‐sectional survey ...on cholelithiasis. Participants were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire on family and personal history and underwent a physical examination and blood chemistry. Statistically significant associations were established by univariate analysis of the age‐standardized data and by step‐wise multiple logistic regression.
At univariate analysis, increasing age, serum triglycerides and number of cigarettes smoked per day, and decreasing high‐density lipoprotein‐cholesterol were the conditions associated with the presence of gallstones in men. Age and parity were the correspondent associations in women. After controlling by multiple logistic regression, a different pattern of associated conditions emerged. In men, only age and serum triglycerides showed a significant positive association with gallstones, which was independent of other variables. In women, the presence of gallstones was independently associated with increasing age, number of pregnancies, body mass index and serum triglycerides, and with decreasing total (and low‐density lipoprotein) cholesterol. The latter association was curvilinear in shape.
The conditions associated with a history of cholecystectomy differed from those observed in subjects with gallstones, with the exceptions of age, in both sexes, and high serum triglycerides, in women. Fasting blood glucose levels were higher in women with a history of cholecystectomy than in those with or without gallstones, both at univariate and multiple logistic regression analyses.
The ongoing prospective evaluation of the populations under study will elucidate the potential role of the epidemiological associations found in men and women as risk factors for the development of gallstones.
A population of male civil servants in Rome, Italy, was investigated to determine the prevalence of symptomatic and asymptomatic gallstone disease. Field activities started in December, 1982 and were ...concluded in July, 1984. Diagnosis was made using real‐time ultrasonography. Participation in the study was 71.5%. Prevalence of gallstone disease was 8.2% and increased with age from 2.3% in the 20‐ to 25‐year‐old age group to 14.4% in the 60‐ to 69‐year‐old age group, based on both presence of gallstones and history of cholecystectomy. About one‐third of the subjects with gallstone disease had previously been submitted to cholecystectomy. Only 7.7% of the subjects with presence of gallstones complained of at least one episode of biliary pain in the preceding 5 years. Frequency of “minor” dyspeptic symptoms was not different between men with and those without gallstones.
In the light of the high prevalence of non organ-specific autoantibodies in chronic hepatitis C, the possibility that such a finding may represent the consequence of a viral, autoimmune or ...overlapping disease should be considered, which may in turn require a different therapeutical approach. It is known, anyway, that the diagnosis of autoimmune hepatitis is based on a set of epidemiological, clinical, biochemical, histological criteria and autoantibody pattern. In 113 cases of chronic hepatitis with HCV infection, we determined the presence of non organ-specific autoantibodies anti-nuclear (ANA), anti-smooth muscle (SMA), anti-liver-kidney microsomal antibodies (LKM), anti-mithocondrial antibodies (AMA) and described the epidemiological, clinical, biochemical, histological characteristics and therapeutic response to interferon. 40 patients (35%) exhibited non organ-specific autoantibodies: 25 patients were SMA positive (Vasal pattern), 4 ANA positive (Speckled pattern), 7 ANA (Speckled pattern) + SMA (Vasal pattern) positive and 4 LKM positive. All subjects with HCV infection and autoantibodies did not display additional criterias of autoimmunity, including the same outcome to interferon therapy when compared to HCV positive patients without autoantibodies. The failure to determine clinical features, associated to autoimmunity in HCV positive patients with autoantibodies, suggests that autoantibody occurrence may represent a fortuitous event during the course of HCV infection.
Abstract
Human polymorphonuclear cells (PMN) and monocytes (MO) from four ovarian cancer patients and seventeen normal donors were in vitro pretreated with different concentrations (25, 50 and 100IU, ...respectively) of rhGM-CSF. Phagocytosis and killing of PMN and MO as well as PMN polarization were evaluated in cancer patients before treatment (T0) and at the end of each chemotherapeutic cycle (T1, T2, T3 and T4, respectively) in comparison with normal donors. RhGM-CSF did not affect phagocytosis and killing of PMN and MO. On the other hand, this cytokine was per se endowed with the capacity to enhance PMN polarization in both cancer patients (at T2 interval) and normal donors.
Since recent findings have pointed out a key role for reactive oxygen species in kidney diseases, we investigated superoxide anion (O2-) and hydrogen peroxide (H2O2) generation by peripheral blood ...polymorphonuclear cells (PMN) in 20 patients with primary IgA nephropathy (IgAN). Results provided evidence for a significant enhancement of O2- and H2O2 production in IgAN subjects in comparison to patients affected by hypertensive renal injury and healthy donors. Among the IgAN group, the highest oxidative metabolism was observed in patients with severe histologic lesions. On the other hand, in vitro vitamin and/or trace element supplementation to PMN suspensions led to a down modulation of their oxidative responsiveness. These data were further supported by the assessment of O2- release on a kinetic basis. Nutrient pretreatment was in fact able to antagonize either the IgAN-related shortening of the lag period or the increase of maximum O2- production rate following agonist stimulation. Taken together, these findings indicate that an exaggerated PMN oxidative metabolism occurs in IgAN and suggest a potential role for micronutrients in the modulation of PMN metabolic pathway.
Through the three years between June 1995 and June 1998 the authors applied an evaluation schedule for the respiratory surgical risk to all the patients undergoing general surgery. Chest X-ray was ...included in this schedule as a first-level test and it was performed systematically on all the patients. The purpose of the study was to verify the effectiveness of chest X-ray as a routine examination of the respiratory performance, evaluating its predictive value on 1715 cases. The routine employment of this preoperative test on patients resulting risk-free at an accurate clinical anamnestic examination doesn't seem to be justified, basing on the preliminary results achieved. Therefore, chest X-ray should be considered a second-level test, to be performed on the basis of a precise clinical query only. This way a significant health-care cost reduction could be achieved, without affecting the quality of patient's management.
Patients with chronic hepatitis C virus (HCV) infection (530 in toto), and 294 individuals with chronic liver disease of different aetiology, were enrolled in this study to investigate the prevalence ...of monoclonal gammopathies (MG) during chronic liver dysfunction. A monoclonal band was detected in 61 HCV+ patients and in nine HCV subjects only. In both instances, a correlation between MG presence and advanced age or degree of hepatic injury was noted. The prevalence of HCV genotype 2a was higher in HCV+ patients with, rather than in those without, MG. The MG+ HCV+ subjects did not exhibit human leukocyte antigen (HLA)-A33, B8, B65 and DR16 expression, while an increased frequency of DR15 structure was seen in the same group of individuals in comparison with MG- HCV+ patients and healthy donors. These findings suggest a possible relationship between HLA haplotype expression, virus genotypes and the occurrence of MG during the course of chronic HCV infection.
Ipsilateral sympathetic deficits, that is symptoms and signs consistent with a diagnosis of Horner's syndrome, have been described in patients who have undergone thalamotomy for dyskinesia as well as ...for parkinsonism. The present patient material consists of 10 patients with parkinsonism who had undergone stereotactic surgery. Since anhidrosis and miosis are two integral components of Horner's syndrome, forehead sweating and pupillometric response to sympathicomimetic agents have been investigated in this preliminary work. The tests were carried out a considerable time postoperatively. Sweating was stimulated in two different ways: by body heating and by parenterally administered pilocarpine. OH-amphetamine and phenylephrine (an indirectly and a directly acting sympathicomimetic agent) were used in the pupillometric tests. The results were compared with those obtained in a healthy control group. With the OH-amphetamine test, there were some indications of a changed sympathetic activity on the surgical side. However, when comparing these results with those obtained by the phenylephrine test, the inference seems to be allowable that parkinsonian patients operated in this way (target area: ventro-oral thalamic nuclei (Voa and Vop) and the reticular thalamic nucleus) show no definite sympathetic supersensitivity at the late postoperative stage. Our data suggest that the response pattern of the pupils and the sweat glands may be related to the surgical method used and/or to the interval from operation to investigation.
