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Biomedical subjects

S Villa

Publications and source records attributed to S Villa.

At least 73 records · Page 4Linked to original sources
PubMed1987

Role of stress in the exacerbation of chronic illness: effects of clonidine administration on blood pressure and plasma norepinephrine, cortisol, growth hormone and prolactin concentrations.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma norepinephrine (NE), cortisol (CRT), growth hormone (GH) and prolactin (PRL) were studied before and after clonidine (2.5 micrograms/kg i.m.) administration in 193 chronic severely ill patients and 193 normal subjects matched by age and sex. During exacerbation periods (positive manifestations of impairment and progressive disease), the patients showed higher NE, CRT and DBP than the normals or when they were investigated during non-exacerbation periods (92 of the 193). Clonidine induced sharp, marked reductions of NE, CRT and DBP, plus a sudden increase of GH, in all the patients during exacerbation periods. Non-significant reductions of NE, CRT and DBP were observed in normals and in patients during non-exacerbation periods. On the other hand, the GH increase registered during exacerbation periods was of an order of magnitude higher than that registered in normals and in patients during non-exacerbation periods. Significant reduction of SBP was registered both in normals and patients (exacerbation and non-exacerbation periods). Some tendency to PRL lowering was observed during exacerbation periods only. A high positive correlation between NE and DBP (pre- and post-clonidine values) was obtained during exacerbation periods in patients, but not in normals or during non-exacerbation periods in the patients. Similarly, a close negative correlation was obtained between CRT and GH (postclonidine values) during exacerbation periods, but not in normals or during non-exacerbation periods. No significant correlation was found between NE and SBP in any group of subjects. The clonidine-induced changes in GH and CRT observed in the patients during exacerbation periods were in striking contrast to the absence of these changes in depressed patients. This finding is consistent with the low rate of depression (6.7%) registered among our patients during exacerbation periods. The high plasma NE and CRT levels registered in chronic severely ill patients during exacerbation periods reflect a central and peripheral sympathetic hyperactivity, accompanied by an overactivity of the pituitary--adrenocortical axis. The strong reduction of DBP, NE and CRT, along with the sharp and great increase of GH, might be useful as indicators in assessing the exacerbation and progression of severe chronic illnesses.

Arousal↗
PubMed1987

Amantadine potentiates T lymphocyte killing by an anti-pan-T cell (CD5) ricin A-chain immunotoxin.

The studies described in this report demonstrate that 1-adamantanamine hydrochloride (amantadine) is a potent enhancer of the cytotoxic activity of the anti-pan-T lymphocyte (CD5) T101 monoclonal antibody conjugated to purified ricin A-chain (T101-immunotoxin; T101-IT). We also demonstrate that T101-IT in the presence of amantadine does not induce immunotoxin-mediated cytotoxicity in nontarget cells such as human marrow hematopoietic progenitor cells. These results provide further knowledge for the improvement of ex vivo purification of human bone marrow from normal or leukemic T cells prior to allogeneic or autologous stem cell transplantation, respectively. Furthermore, since amantadine has long been employed safely in human therapy, its use in conjunction with immunotoxins might be exploited in vivo.

Amantadine↗
PubMed1987

Specific ex-vivo depletion of human bone marrow T lymphocytes by an anti-pan-T cell (CD5) ricin A-chain immunotoxin.

We studied optimal conditions for ex vivo elimination of mature T cells from human bone marrow by T101 immunotoxin (T101-IT) with criteria applicable to graft-versus-host disease (GVHD) prophylaxis prior to allogeneic marrow transplantation. T101-IT consisted of T101 anti-CD5 monoclonal antibody conjugated to purified ricin A-chain toxin. Marrow mononuclear cells isolated by Ficoll-Hypaque or by fractionation with soybean lectin (SBA- cells) were incubated with T101-IT at 37 degrees C with or without ammonium chloride and/or verapamil as potential enhancers of immunotoxin potency. As controls, competitive inhibition studies with unconjugated T101 or irrelevant IgG2a antibody were carried out. Residual T cells were quantified by limiting dilution in phytohemagglutinin (PHA)-interleukin 2 (IL-2) feeder-cell-containing microcultures and hematopoietic progenitors by CFU-GM assay. We demonstrated that T101-IT in the range of 1-100 nM does not affect early total cell viability; that its delayed cytotoxicity is T-cell-specific, greatly enhanced by ammonium chloride, and moderately by verapamil--which also is not synergistic with ammonium chloride; and that 10 nM X 3 fractionated doses (i.e., added at 0, 1.5, and 3 hr of incubation) in the presence of 10 mM ammonium chloride for 4 hr at pH 7.8 consistently induces 2 log T cell depletion. In addition, if the same T101-IT treatment is preceded by fractionation with soybean lectin (i.e., T101-IT treatment of SBA- marrow cells), 3 log T cell depletion is accomplished. We conclude that T101-IT is highly effective in eliminating T cells from donor grafts. However, data presented here indicate that T101-IT should be associated with additional methods, such as soybean lectin fractionation, to ensure more effective ex vivo T cell depletion and acute GVHD prevention.

Ammonium Chloride↗
PubMed1987

Correspondence between the development of hemopoietic tissue and the time of colony formation by colony-forming cells.

The development of a haemopoietic tissue and the time when colony-forming cells in it formed detectable colonies were studied with in vivo spleen colony-forming units (CFUs) and in vitro high-proliferation-potential colony-forming cells (HPP CFC). Cells that form colonies first are developmentally more mature than those doing so later. Marrow containing mature spleen colony-forming cells formed fewer cells in the femora of recipients than that which contained early colony-forming cells. The growth curve of developmentally early high-proliferation potential-colony-forming cells was steeper than that of later cells. The time period before colony-formation occurs is a property of the colony-forming cell and is not due to regulatory mechanisms in the animal or to regulatory cells in the haemopoietic stroma.

Animals↗
PubMed1986

Vitamin E and vitamin C inhibit arachidonate-induced aggregation of human peripheral blood leukocytes in vitro.

Arachidonate induces aggregation of human polymorphonuclear (PMN) and mononuclear (MNL) blood leukocytes. This is mediated by the lipoxygenase pathway, as it is prevented by lipoxygenase inhibitors and can also be induced by leukotriene B4 (LTB4). Vitamin E and vitamin C have profound effects on the functional state of leukocytes, some of which may involve the lipoxygenase pathway. This study shows that both vitamins inhibit arachidonate-induced aggregation of PMN and MNL, in a concentration-dependent way. BW-755, previously shown to inhibit arachidonate-induced PMN and NML aggregation, was found to potentiate the inhibitory activity of both vitamins. When LTB4 was used as an aggregating agent, vitamin E markedly inhibited PMN and MNL aggregation, whereas vitamin C was ineffective. The prevention of PMN and MNL aggregation by vitamin E might account, at least partially, for the reported beneficial effects of vitamin E supplementation in some experimental syndromes characterized by leukocyte activation.

Arachidonic Acid↗
PubMed1985

Treatment of ulcerative colitis with clonidine.

In the present 30-week, double-blind study of 45 ulcerative colitis (UC) patients treated with prednisone, sulfasalazine, clonidine, or placebo, we found that clonidine (an alpha 2 agonist) and prednisone were effective in treating idiopathic UC. Both drugs were more effective than sulfasalazine. Furthermore, clonidine potentiated prednisone and sulfasalazine effects. Clonidine was chosen because its effect on distal colon motility is similar to thioproperazine, an antipsychotic drug that, despite many adverse effects, possesses powerful anti-UC properties. Rating scales were outlined in order to evaluate clinical, endoscopic, histologic, and radiologic changes. Plasma cortisol levels, sedimentation rate, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, and other biochemical parameters were determined to assess the efficacy of each drug. Distal colon motility changes were also assessed. All our UC patients showed raised cortisol plasma levels and low sigmoidal tone during relapse periods. These parameters were reversed during remission periods. Peripheral and central mechanisms are discussed.

Adolescent↗
PubMed1985

Effects of clonidine on blood pressure, noradrenaline, cortisol, growth hormone, and prolactin plasma levels in high and low intestinal tone subjects.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE), cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 46 normal subjects, 28 high intestinal tone (high IT) and 18 low intestinal tone (low IT), before and after the administration of a single intramuscular dose of clonidine (2.5 micrograms/kg). High IT subjects had lower mean values of DBP than low IT subjects, and basal NE was significantly greater in low IT than in high IT subjects. A negative correlation between NE and IT values was found for the high IT, but not for the low IT group, during the preclonidine periods. The drug reduced SBP in high IT, whereas it reduced SBP plus DBP and NE in low IT subjects. Clonidine induced significant reductions of CRT and increases of GH in both groups; furthermore, a slight but significant reduction of PRL was registered in high IT group. The drug also induced increase of distal colon tone in high IT subjects and suppressed phasic activity (waves) in low IT subjects. While a significant positive correlation was found between NE and DBP in low IT subjects during postclonidine periods, no correlation was found between the two parameters in high IT subjects. Other significant positive (+) and negative (-) correlations during postclonidine periods were: CRT/GH (-), CRT/PRL (+), and GH/PRL (-) in high IT subjects; NE/CRT (+), NE/GH (-), CRT/GH (-), CRT/DBP (+), and GH/DBP (-) in low IT subjects. Finally, significant negative correlation was found between NE and distal colon tone during postclonidine periods in high IT subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effects of clonidine on blood pressure, noradrenaline, cortisol, growth hormone, and prolactin plasma levels in high and low intestinal tone depressed patients.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE) plasma levels, cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 26 high intestinal tone (high-IT) and 24 low intestinal tone (low-IT) depressed patients, before and after the intramuscular injection of clonidine (2.5 micrograms/kg). A positive correlation was found between NE, DBP, and Hamilton Depression Rating Scale (HRS) values in low-IT depressed patients, while a negative correlation was found between HRS/IT and NE in high-IT depressed patients. Although clonidine induced significant reduction of SBP in both groups, the drug reduced DBP and NE in the low-IT group, only. CRT mean level was greater in the high-IT than in the low-IT depressed group. However, clonidine was unable to induce changes in CRT, GH, and PRL mean levels in any depressed group. Our results suggest that the clonidine-induced DBP reduction is a reliable index of sympathetic activity in depressed patients and that both parameters (DBP and IT) are useful physiological markers to differentiate two types of depressive syndromes.

Blood Pressure↗
PubMed1985

Detection of the common acute lymphoblastic leukaemia antigen (CALLA) on B cells from human fetal tissues. A multiple phenotypic characterization.

Fetal bone marrow liver and spleen of gestational age 15-20 weeks contain CALLA+, HLA-DR+ lymphoid cells. We show that a proportion of them expresses surface membrane immunoglobulins (SIg) as well as B cell differentiation antigens. A multiple phenotypic analysis reveals that CALLA+ fetal B cells are: HLA-DR+, SIg+, FMC8+, BA1+, Y29.55+ or Y29.55-, B2+, TdT-. Tissue specific phenotypic differences concern the expression of B7 and HLA-DC on spleen but not on bone marrow B cells. This study indicates that the distribution of the CALL antigen across the B cell committed lineage is much wider in fetal than neonatal life since CALLA+B cells have not yet been detected in bone marrow and peripheral blood of normal infants and adults. In addition, the interpretation of our phenotypic data suggest that fetal bone marrow B cells are more immature than those present in the spleen, thus, further supporting the evidence that the bone marrow is the organ of B cell lymphopoiesis.

Antigens, Neoplasm↗
PubMed1985

[Action of radiation on the lung. Classic concepts and current interpretations].

The effects of irradiation on the pulmonary system are analyzed according to the classical radiobiological theories and the new ones. Special emphasis is put on the lineal-quadratic model which predicts the possibility of a greater tumor control without increasing the damage to the normal lung tissue, based on the differences between the survival curves for acute and late effects of irradiation. The clinical applications of the new radiobiological concepts can be carried out in the treatment of lung cancer and other neoplasms, especially those using total body irradiation.

Humans↗
PubMed1984

Characterization of the response of human thymocytes and blood lymphocytes to the synergistic mitogenicity of 12-O-tetradecanoylphorbol-13-acetate (TPA)-ionomycin.

The combination of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore ionomycin is synergistically mitogenic for human fetal and infant thymocytes as well as peripheral blood lymphocytes. Optimal mitogenic stimulation is achieved when TPA and ionomycin are used at doses of 0.5-1 ng/ml and 0.5-1 microgram/ml, respectively. Phenotypic analysis and cell sorting show that the thymocytes responsive to the mitogen have a mature or medullary phenotype (T1+, T3+, T11+, T6-, HLA-A,B++, [TdT]-); similarly in blood the T cell subsets (T11+, T4+ and T11+, T8+) are selectively responsive to TPA-ionomycin. Both activated lymphocytes and thymocytes express HLA-DR antigens as well as activation antigens such as T9, T10 and T cell activation antigen. T cells activated by TPA-ionomycin can be grown for periods of up to 50 days without addition of exogeneous interleukin 2. The observations may have implications for the membrane-associated signals involved in T cell growth and proliferation.

Cell Division↗