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Biomedical subjects

A De Maria

Publications and source records attributed to A De Maria.

At least 55 records · Page 3Linked to original sources

Phenotypic and functional characteristics of tumor-associated lymphocytes in patients with malignant ascites receiving intraperitoneal infusions of recombinant interleukin-2 (rIL-2).

In the course of a phase I trial, in which recombinant IL-2 (rIL-2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on "tumor-associated lymphocytes" (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu-7, OKM1 and WT-31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rIL-2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL-2 receptor (Tac), or LAK-1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural-killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN-gamma was detected in the ascitic fluid following rIL-2 infusion. T-cell clones derived from the patient were analyzed for the IFN-gamma production. While only approximately 40% of PB-derived control clones produced medium to low amounts of IFN-gamma, all of the TAL-derived clones produced medium to high amounts of the lymphokine.

Ascites↗

Whole blood collection on filter paper is an effective means of obtaining samples for human immunodeficiency virus antibody assay.

The suitability of collecting whole blood specimens on filter paper disks for HIV antibody assay was evaluated. ELISA and Western blot assay results were in complete agreement for serum and blood spot disk samples. Sensitivity of the two methods was tested using diluted whole blood and sera from HIV-seropositive individuals. Results demonstrate that ELISA and Western blot assays performed on punched-out disks of the blood-impregnated papers had the same sensitivities as those obtained with serum samples. This study suggests that whole blood collection on filter paper can be effectively substituted for serum sampling in HIV antibody screening programs.

Antibodies, Viral↗

CD3+4-8-WT31-(T cell receptor gamma+) cells and other unusual phenotypes are frequently detected among spontaneously interleukin 2-responsive T lymphocytes present in the joint fluid in juvenile rheumatoid arthritis. A clonal analysis.

T lymphocytes (E rosetting cells) isolated from the joint fluid of four patients with juvenile rheumatoid arthritis (JRA) were first analyzed for surface antigen expression. Approximately 15% of cells were CD25+ (interleukin, IL, 2 receptor positive), in addition, a remarkable proportion of cells expressed the CD2+3- phenotype. CD3+ cells outnumbered the sum of CD4+ and CD8+ cells as well as the cells reactive with the WT31 monoclonal antibody (which recognizes a framework determinant of the alpha/beta T cell receptor). Purified T cells were cloned under culture conditions (1% phytohemagglutinin, PHA plus IL2) which allow clonal expansion of most peripheral blood T lymphocytes. Under these conditions proliferating cells ranged from 25 to 65%; clones (derived from microcultures containing 0.5 or 0.25 cells/well) were tested for cytolytic activity against P815 cells (in the presence of PHA) or against the natural killer (NK)-sensitive K562 target cells. Fifty-four percent and 73% of clones obtained from the two patients with the polyarticular form of the disease displayed cytolytic activity in the lectin-dependent assay. Cytolytic clones were 22 and 29% in the two patients with single joint involvement. About half of all cytolytic clones displayed NK-like activity. Surface antigen analysis revealed that, in addition to conventional CD3+4+8- and CD3+4-8+, a noticeable fraction of clones (50/202) displayed unusual surface phenotypes. In particular, 33/50 coexpressed CD4 and CD8 antigens; 7/50 were CD2+3-4-8- and displayed NK-like activity; 10/50 expressed CD3 but lacked both CD4 and CD8 antigen and did not react with the WT31 monoclonal antibody. In order to allow selective growth of IL2-responsive cells, T lymphocytes were also cloned directly in IL2. As much as 57% of all clones thus obtained (48/84) displayed cytolytic activity. Moreover, about half expressed unusual surface phenotypes including CD2+3-4-8-, CD3+4+8+ and CD3+4-8-WT31-. Given the accumulation at the site of the joint involvement of unusual T cells, most of which displayed cytolytic activity and were likely to represent cells activated in vivo (IL2 responsive), one may speculate that these cells may be involved in the injury process.

Antigens, Differentiation, T-Lymphocyte↗

Luteinizing hormone pulsatile secretion and pituitary response to gonadotropin releasing hormone and to thyrotropin releasing hormone in male epileptic subjects on chronic phenobarbital treatment.

Endocrine changes have been reported in treated epileptic subjects, who often exhibit sexual dysfunctions, but the endocrine effects of single antiepileptic drugs have not been completely elucidated. In this study we have investigated the influence of phenobarbital (PB) on adenopituitary function and on peripheral sexual steroid pattern in 8 epileptic males. Chronic PB treatment does not modify luteinizing hormone (LH) pulsatile secretion. In the same subjects, LH and follicle stimulating hormone (FSH) response to Gonadotropin Releasing Hormone was blunted with respect to healthy controls both in terms of absolute values and of secretion areas. No difference was found in prolactin (PRL) response to Thyrotropin Releasing Hormone. In the epileptic group a significant increase in the levels of sex hormone binding globulin and a consequent decrease of the percent free testosterone have been observed. PB treatment also significantly lowers 17-beta-estradiol mean levels. These data suggest that PB independently affects both gonadotropin secretion and peripheral steroid pattern.

Adult↗

Changes in the dopaminergic control of prolactin secretion and in ovarian steroids in migraine.

Prolactin (PRL) responses to dopamine (DA) blockers and to direct and indirect DA agonists have been studied in 23 healthy women, 17 women with catamenial migraine and 17 with non-catamenial migraine in both their follicular and luteal phases. PRL responses to the DA blockers were greater in the follicular phase of both migraine groups than in controls. The inhibitory effect of nomifensine on PRL secretion was dampened in the follicular phase of both migraine groups. These findings demonstrate an increased PRL reserve in migraine and suggest the existence of a dopaminergic supersensitivity of the lactotrophic postsynaptic DA receptors. The impaired inhibitory effect of nomifensine on PRL secretion hints at a decrease of the presynaptic DA content in tuberoinfundibular DA neurons. In migrainous women 17-beta-oestradiol levels are higher in both ovarian phases, whereas progesterone concentrations and the progesterone to oestradiol ratio are lower than in healthy subjects in the luteal phase. These data suggest the existence of a change in the oestrogen-dependent modulation of pituitary DA receptors.

Adult↗

Benserazide effects on growth hormone, prolactin, and thyrotropin in normal and acromegalic man.

The effect of benserazide administration on the secretion of GH, PRL, and TSH has been considered as an index of dopamine regulatory actions. Nine acromegalic patients and nine normal subjects were given a single 125 mg oral dose of benserazide, and serum GH, PRL, and TSH were determined by RIA methods every 30 min for 4 h. Benserazide did not alter GH values either in normal subjects or in acromegalic patients. A significant increase of serum PRL was found in both groups, and the increase was similar in normoprolactinemic and in hyperprolactinemic acromegalic patients. A significant increase in TSH levels was found only in acromegalic patients. Thus, a decrease in dopamine outside the blood-brain barrier did not affect GH secretion, whereas PRL secretion was changed in the acromegalic as well as in the control group.

Acromegaly↗

Pathophysiology of bacteremia.

Despite the frequency and importance of both nosocomial and "community-acquired" bacteremia, definitive information concerning crucial pathophysiologic events in human bacteremia remains sparse. An extensive variety of clinical manifestations, such as fever, rigors, shock, altered circulatory dynamics, cutaneous manifestations changes in the coagulation, complement, and other mediator systems, and effects on the lungs, heart, kidney, liver, and other end organs, have been described, but it is difficult to determine the relative frequency of these events in bacteremia caused by different species. The extensive number of bacterial species capable of producing bacteremia and variations in the type of presentation, such as acute, asymptomatic, and chronic, even when bacteremia is produced by the same species, undoubtedly contribute to this difficulty and suggest that a variety of pathophysiologic mechanisms occur in various bacteremias. In contrast, the relative frequency of various manifestations and some pathophysiologic mechanisms have been better delineated in Gram-negative bacteremia. The development of bacteremia enhances the lethality of most types of localized infection and several studies have demonstrated a relation between the magnitude of bacteremia and the outcome of the disease. Among various pathophysiologic alterations, mechanisms involved in the production of fever have been delineated most clearly. Fever appears to reflect a "common pathway" with almost all infectious agents and results from release of endogenous pyrogen from phagocytic cells. Endogenous pyrogen regulates the thermostatic setting of the body through its effect on the anterior hypothalamus. Endogenous pyrogen seems identical with Interleukin 1 and exerts a variety of other biologic activities. An extensive number of bacterial components have been proposed as "effectors" and an equally large number of endogenous substances proposed as "mediators" of the pathophysiologic events in bacteremia. The importance of many of these effectors and mediators has been postulated largely on the basis of in vitro and animal studies. The lack of critical clinical studies hampers extrapolation of these experimental studies to human bacteremia. The development of more effective therapy for the complications of bacteremia, such as shock, will continue to be hampered until the mechanisms involved in the production of those pathophysiologic events that are crucial determinants of outcome have been delineated more precisely in human disease.

Bacterial Toxins↗