Clinical features of benign infantile convulsions: familial and sporadic cases.

The authors describe the so-called benign convulsions of infancy and confirm the existence of benign nonfamilial infantile convulsions during the first 2 years of life and their benign course. The authors evaluated 58 patients: 17 subjects had a family history of benign epilepsy, and 41 did not. No clinical differences were observed between the two groups.

Interleukin-6 release in the hepatic blood outflow during normothermic liver ischaemia in humans.

BACKGROUND: Liver surgery techniques have consistently improved and normothermic ischaemia of the liver is considered to be a safe procedure to reduce intraoperative haemorrhage. Hepatic failure, however, remains a significant complication. In liver ischaemia-reperfusion injury, cytokines play a key proinflammatory role. Cytokines may be part of the intercellular signalling that leads to recovery or to failure after major surgery. Moreover, they could be potential predictors of the outcome. Modulation of the pattern of cytokine response in the early postsurgery period could represent a new approach to minimise the impact of these procedures. AIMS: The aim of our study was to analyse the cytokine pattern in the hepatic blood outflow in patients undergoing surgical intervention of partial liver resection with clamping of the hepatic pedicle and liver ischaemia, and to correlate the cytokine behaviour with clinical parameters. PATIENTS: We studied eight patients (mean age 55 years) who underwent surgical intervention of liver resection during vascular exclusion of the hepatic pedicle. Patients were monitored for haemodynamic and haematological parameters during the pre-, infra- and postoperative period. METHODS: IL-I alpha, IL-6, TNF-alpha and IFN-gamma were assayed from peripheral and central vein blood at different times. Blood samples for cytokine assays were also drawn from the supra-hepatic veins after clamping of the porta hepatis. RESULTS: We found a significant increase of the IL-6 levels in the supra-hepatic samples during liver ischaemia, while the trend with IL-1alpha was less clear; IFN-gamma and TNF-alpha were undetectable with the methods used. IL-6 levels appeared to correlate positively with bilirubin and gamma-GT levels and negatively with the degree of acidosis. CONCLUSIONS: Our study confirms that during surgical ischaemic stress there is an increase of IL-6 serum levels more relevant in supra-hepatic vein blood. Cytokines could contribute to modulate the inflammatory response to liver ischaemia.

Modulation of X-ray-induced damage recognition and repair in ageing human peripheral blood mononuclear cells by an interleukin-6-type cytokine.

We have investigated the effects of an interleukin (IL)-6-type cytokine on the DNA-binding activity of ku and on unscheduled DNA repair in X-ray-treated peripheral blood mononuclear cells (PBMC) from human subjects of different ages. The cytokine used, called K-7/D-6, is an IL-6 variant with increased in vivo and in vitro biological activity compared to the wild type molecule. Ku is the DNA-binding component of the DNA-dependent protein kinase (DNA-PK). It binds the ends of various types of DNA discontinuity and is involved in the repair of DNA breaks caused by V(D)J recombination, isotype switching, physiological oxidation reactions, ionizing radiation and some chemotherapeutic drugs. The ku-dependent repair process, called non-homologous end joining, is the main DNA double strand break repair mechanism in irradiated mammalian cells. Results show that K-7/D-6 significantly increases DNA-binding activity of ku in irradiated PBMC from young but not from elderly subjects. However, K-7/D-6 is able to induce unscheduled DNA repair in irradiated PBMC from both young and elderly subjects. These effects of K-7/D-6 are relevant to the mechanisms of the cellular response to DNA damage.

Neuropeptide Y plasma levels and immunological changes during academic stress.

Academic stress is a good model of psychological stress in humans for studying psychoneuroimmune correlations. We looked for correlations between psychological scores, immune tests and plasma levels of cortisol and neuropeptide Y (NPY). A group of medical students were evaluated at the beginning of the academic year (Baseline) and the day before an examination (Stress). They underwent evaluation by The Profile of Mood States (POMS), The Malaise Inventory, The Self Efficacy Scale and A Global Assessment of Recent Stress (GARS). The lymphocyte subsets, the lymphocyte proliferative response and the cytokine production were also evaluated. We detected modifications of some psychological test scores between the Baseline and Stress evaluation, a significant reduction of lymphocyte proliferation, IL-2 production and percentage of the lymphocyte CD19, and an increase in plasma cortisol levels during stress. The lymphocyte proliferation negatively correlated with the POMS score as well as the percentage of CD16+ cells with NPY plasma levels. NPY levels were not different from Baseline. The emotional and mood states seem to influence immunity. Copyrightz1999S.KargerAG,Basel

Effect of age on DNA binding of the ku protein in irradiated human peripheral blood mononuclear cells (PBMC).

DNA binding of the ku protein was investigated in peripheral blood mononuclear cells (PBMC) from 24 subjects of different ages (20-89 years old) displaying age-related changes in DNA repair, mitotic responsiveness, and cytokine production. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the earliest steps of DNA damage recognition. DNA binding of ku 70/80 was found unchanged in normal PBMC from aging subjects but progressively declined in x-ray-irradiated PBMC from young to adult, and elderly subjects. This finding was concomitant with the age-related fall of DNA repair in the whole population.

Characteristics of gastric-vein lymphocytes with regard to the immune response to Helicobacter pylori.

BACKGROUND: Between peripheral blood and tissue-infiltrating lymphocytes there is an intermediate compartment, the blood of the organ-draining vessels, which could show unusual features. The aim of the present study was to analyse the characteristics of the lymphocytes from the stomach-draining vessels and the cytokine secretion by these lymphocytes. The CagA-mediated lymphocyte activation in Helicobacter pylori-infected subjects and the humoral response to this antigen were evaluated and correlated with clinical data. METHODS: We studied lymphocyte proliferation either with mitogens or with the CagA antigen and cytokine production and IgG anti-CagA by means of an enzyme-linked immunosorbent assay in peripheral blood and gastric-vein blood obtained during surgical intervention. RESULTS: We showed higher proliferative response and cytokine production in lymphocytes from the gastric vein. The mitogenic response to the CagA antigen was highly specific but poorly sensitive for the H. pylori infection in both the compartments. The overall cytokine profile in our patients affected by non-ulcer disease was of the Th0 type. CONCLUSIONS: Gastric-vein-derived lymphocytes seem to show unusual features, as they behave like peripheral blood lymphocytes but show higher responses to all the tested stimuli. It is possible that the interaction of the lymphocytes with the mucosal environment could activate the synthetic mechanisms, making the cells more 'responsive' to the stimulation. The CagA antigen is able to induce a specific T-lymphocyte response and is therefore a valid candidate antigen for the development of a vaccine.

Psychoneuroimmunology and aging.

BACKGROUND: The senescence of the immune system is a complex phenomenon, characterized by impairment of several lymphocyte activities and generally considered a state of immune dysregulation. Aging is a condition associated with many social changes likely to induce psychological stress, which is often perceived as uncontrollable and can lead, in some cases, to clinically relevant depression. In the recent years a growing interest has been raised for the study of bidirectional interactions between the central nervous system and the immunological network (psychoneuroimmunology). OBJECTIVE AND METHODS: We analyzed the possibility that chronic psychological distress and depression could worsen some immune functions in the aged. We postulate the neuroendocrine mechanisms of psychoimmune interaction, analyzing both the human and animal studies focused on aging. RESULTS: The data from the literature reviewed suggest a significant impact of affective disorders on immune functions in the elderly subjects. This psychoimmune imbalance appears particularly important when the studies are carried out in otherwise healthy aged people. CONCLUSIONS: Here we reviewed the relationships between psychological stress and depression and immunological functions, with particular regard to those aspects pertinent to the aging process. The clinical relevance of these interactions remains to be elucidated, but the high frequency in the aged of autoimmune, infectious, and neoplastic diseases suggests to focus on the psychoneuroimmune interactions in the old age. We also propose some outlines for future studies concerning psychoneuroimmunology and aging.

Changes in the amount and level of phosphorylation of p56(lck) in PBL from aging humans.

The effects of aging on the activation of the cytoplasmic tyrosine protein kinase p56(lck) have been investigated in PBL from adult and elderly subjects upon activation with mitogens or different co-stimuli. Results show that the amount and phosphorylation of p56(lck) are reduced in PBL from elderly as compared to adult subjects. This finding suggests that alterations in p56(lck) may contribute to the age-associated loss of some T cell functions, such as proliferation and IL-2 production, which are found decreased in PBL from old individuals. However, p56(lck) seems irrelevant to the production of IFN-gamma and IL-4 which were both found increased in the PBL from old subjects, as expected from the relative expansion of memory versus naive T cell subpopulations in aging.

Cell proliferation and ku protein expression in ageing humans.

Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku protein in a human population of 43 subjects of different ages. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the early steps of DNA damage recognition. In the present study, PBL from subjects of different ages were PHA-activated to evaluate the stimulation index and the production of Th1- and Th2-type cytokines. Moreover, nuclear extracts were obtained from activated lymphocytes to evaluate by a gel retardation assay the presence and the functional activity of the heterodimer ku 70/80. Our results indicate that ageing affects the mitotic responsiveness and cytokine production to a significant extent, but only marginally the expression of ku 70/80. These findings suggest that the age-related impairment in DNA repair mechanisms are only in part related to the reduced expression of ku protein able to recognize DNA damage.

Plasma thrombin-antithrombin complexes, latent coagulation disorders and metastatic spread in lung cancer: a longitudinal study.

In patients affected with different tumours, disorders concerning clotting are frequently observed. The biological processes leading to coagulation are probably involved in the mechanisms of metastasis. We studied plasma levels of thrombin-antithrombin III complexes (TAT) in 90 patients affected with lung tumours subgrouped in small cell and non-small cell (NSC) lung cancer: 17 patients had no evidence of disease after surgery (NE); the remaining 73 patients were divided according to the absence (LOC) or the presence (META) of metastases. All the patients were followed up for several months. In all the lung cancer patient groups, at the beginning of the study we detected TAT levels that were higher than in controls. During the follow-up period, the NSC-NE patients with no recurrence of the disease as well as the NSC-LOC patients responding to the treatment had a decrease in TAT levels (p < 0.01 and p < 0.05, respectively). The NSC-META patients with progression of their disease had, in contrast, an increase in TAT levels (p < 0.01). Our data reveal the presence of 'latent coagulation disorders' as assessed by the presence of high TAT levels in the majority of lung cancer patients. The follow-up study indicates that in the NSC group, a relation exists between coagulation activation and rate of tumour progression and/or response to treatment. In cancer patients the early detection of coagulation disorders could also allow, therefore, the prevention of thromboembolism and/or haemorrhage by administration of appropriate treatment.

Neuroimmunomodulation and psychoneuroendocrinology: recent findings in adults and aged.

In recent years the relationships among immune, endocrine and nervous systems have been extensively studied, and grouped in a new research field: psychoneuro-immunoendocrinology. Since ancient times its has been known that, in humans, mood as well as environmental influences could affect health. In the late '70s, only, evidence of bi-directional pathways has been achieved, first in animal models and, later on, in humans. We reviewed current knowledge on neuroimmunomodulation, concerning the influence of stress and psychological status on immunity as well as neuroendocrine modulation by the immune system, reporting some data obtained from our studies. Particularly, having detected a relevant impairment concerning most of the parameters studied, we emphasized the effects of depressive disorders on immune function in the elderly.

Occupational dermatitis in animal feed mill workers.

In an epidemiological study of occupational dermatitis in 15 different northern Italian animal feed mills, 204 workers were interviewed, examined and patch tested to 34 allergens, selected from the additives most commonly used in the animal feed mills under consideration. The prevalence of occupational contact dermatitis was 13.7% (28/204): 7.8% (16/204) irritant contact dermatitis and 5.8% (12/204) allergic contact dermatitis from animal feed additives. Among the latter, there were sensitizations, to our knowledge hitherto unreported in the literature: to indigo carmine (2 cases), monensin sodium (1 case), thiabendazole (1 case), methylchlorpindol (1 case) and amprolium hydrochloride (1 case). 3.9% (8/204) of the workers complained only of pruritus sine materia on exposed areas of the body. Contact dermatitis increased with respect to duration of employment: the difference in the rate of contact dermatitis between workers employed in animal feed mill for greater than 10 years and those employed for less than 10 years was statistically significant (p less than 0.05). 6.8% (14/204) had latent sensitivity, which was more frequent in workers with less than 1 year of employment with respect to more experienced colleagues.