Soluble interleukin-2 receptor release defect in vitro in elderly subjects

The evidence from several studies indicates that as individuals age, they may display immune dysfunctions, mostly T cell dysfunctions. Recently, a soluble form of the receptor for interleukin-2 (IL-2) (sIL-2R) has been demonstrated in human sera and in vitro stimulated culture supernatants from human T lymphocytes. In the present paper, we report in vitro sIL-2R production from peripheral blood mononuclear cells in elderly subjects. The results show that no difference exists for unstimulated cultures, whereas after mitogen stimulation the elderly subjects showed the lowest values compared with young ones. These findings suggest that sIL-2R may provide a new tool for the study of T lymphocyte dysfunctions in old age.     

Endoscopic stapling diverticulotomy: an audit of difficulties, outcome, and patient satisfaction.

OBJECTIVE: To evaluate the procedure in terms of technical difficulties, patient satisfaction, symptom relief, recurrence, and further management. STUDY DESIGN: Retrospective study including 41 patients who underwent endoscopic stapling diverticulotomy. Clinical notes were reviewed, and patients were sent a patient satisfaction questionnaire. Statistical analysis was done using the chi(2) square test. SETTING: Teaching hospital. RESULTS: Larger pouches had the best results; 81.578% were satisfied with the surgery, and 86.84% had improved swallowing. Complications presented in 6 patients (15%), including a perforated pouch and an esophageal perforation. Complications were more frequent in small pouches. CONCLUSIONS AND SIGNIFICANCE: Endoscopic stapling diverticulotomy offers rapid recovery in most patients, with early oral intake and short hospital stay. There is a high degree of symptoms relief, and the patient's satisfaction rate is high. The assessment of the pharyngeal pouch size is an important factor when deciding the best management for a patient with a pharyngeal pouch.     

Curietherapy using a ruthenium and iridium disk in the treatment of choroid melanoma

Following the experience of the German authors, the treatment of choroidal melanoma with ruthenium 106 disk was introduced in Lyon. Between 1983 and 1988, 127 patients were treated. Results are analysed on a group of 84 patients followed 18 months and more. In 72 cases a reduction of thickness was noted. It was complete in 33 cases. Enucleation was performed in 10 patients due to no response or regrowth. In 3 cases the tumor was sterilized. Five patients died of metastases, and 73 are alive, 3 of them with liver metastases. An afterloading iridium template disk was used in 8 patients. 4 of them with a tumor thickness between 6.5 and 8 mm had a good response. Edema of the fovea was observed in 21% of cases, while cataracts were very unusual with Ru 106. An enucleation was performed in 6 patients because of a complication. A useful vision may be preserved in 60% of cases. The scleral tolerance dose is close to 1,500 Gy. These results are in agreement with those of the literature and are considered to be satisfactory for tumors not exceeding 5 to 6 mm in thickness. If the tumor is located close to the fovea or the papilla, and/or if the thickness is 8 mm or more, proton beam could be a good alternative.     

Ontogenetic Development of 5-HT1D Receptors in Human Brain: An Autoradiographic Study

The pattern of pre- and postnatal appearance of 5-HT_1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [¹²⁵I]GTI (serotonin O -carboxymethyl-glycyl-[¹²⁵I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT_1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [¹²⁵I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT_1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT_1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT_1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period.     

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.     

Human tonsil,blood and bone marrow in vivo-induced B cells capable of spontaneous and high-rate immunoglobulin secretion in vitro: Differences in the requirements for factors and for adherent and bone marrow stromal cells,as well as distinctive adhesion molecule expression

Human B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2–3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re-addition experiments. Stromal BM cells supported linear IgG secretion by non-adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor-α, interleukin-6 or fibronectin + interleukin-6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA^+/? CD44⁺ CD49d⁺ CD49e^? Leu-8^+/?, the blood cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8⁺ and the BM cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8^?. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.     

Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort.

BACKGROUND: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study. METHODS: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs. RESULTS: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00). CONCLUSION: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer.     

Degradation of extracellular matrix proteins (fibronectin, vitronectin and laminin) by serine-proteinases isolated from Lonomia achelous caterpillar hemolymph.

Lonomia achelous is a caterpillar distributed in southern Venezuela and in northern Brazil that causes an acute hemorrhagic syndrome in people who have contact with its bristles. The effect of the crude hemolymph and its chromatographic fractions (FDII, Lonomin V and Lonomin V-2) on extracellular matrix proteins was studied. The chromatographic fractions show activities similar to plasmin and urokinase. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both lonomins appear as a protein band of 25 kDa under reduced conditions. By exclusion chromatography, the molecular weights of Lonomin V and Lonomin V-2 were 26.5 and 24.5 kDa, respectively. Fibronectin, laminin and vitronectin were degraded by all venom components. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under reduced conditions, shows that lonomins degrade fibronectin in four main fragments of 116, 60, 50 and 30 kDa. Molecular exclusion chromatography in native conditions shows that the molecular masses of these fragments are > or = 300, 62 and 27 kDa. The proteolytic effect of lonomins was abolished by benzamidine/HCl, iodoacetic acid and aprotinin. The extracellular matrix protein degradation together with the fibrino(geno)lytic activity of hemolymph and its fractions could explain, in part, the hemorrhagic syndrome, and the wound dehiscence in persons who have had contact with the L. achelous caterpillar.