PubMed Health⌕ Search

Biomedical subjects

S Marini

Publications and source records attributed to S Marini.

At least 55 records · Page 3Linked to original sources
PubMed1991

A new monoclonal antibody to an age sensitive band 3 transmembrane segment.

The appearance of band 3 structural modifications related to aging could be evidenced by means of monoclonal antibodies against senescence antigen. Hence in the attempt to provide an immunological marker of erythrocyte aging, we raised a monoclonal antibody against native band 3 (B6 MoAb), which seems to detect differences in the band 3 molecule from erythrocytes of different ages separated by density gradient. Densitometric evaluation of immunoblotting patterns indicates that the in vivo aging is associated with band 3 monomer degradation. The Percoll separated fractions show a significant increase of those proteolytic fragments that bind the B6 antibody. Finally, protease digestions of unsealed membrane ghosts have been performed to test the binding site of the B6 antibody on the band 3 molecule. The data show that the B6 antibody binds a 19 KDa chymotryptic-tryptic fragment which corresponds to a segment of the looped membrane domain whose steric structure appears to be sensitive to age.

Animals↗
PubMed1991

Immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a potent anti-HIV nucleotide analogue, on in vivo murine models.

In order to evaluate the influence of antiviral nucleoside analogues upon the natural immune system, we investigated the immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a nucleotide analogue with potent anti-HIV and anti-herpes activity, in a murine system. C57BL/6 mice were inoculated intraperitoneally with 10, 25 and 50 mg PMEA/kg. Mononuclear cells were isolated from their spleens, and some natural immune functions were evaluated. The results show that PMEA significantly increases the levels of natural killer (NK)-cell cytotoxicity. We also found that alpha/beta IFN production was substantially increased in PMEA-treated mice, while both IL-1 and IL-2 production was decreased. Thus, PMEA can increase some natural immunity functions, such as NK activity and IFN production. These results suggest that PMEA might be active in vivo against HIV and herpes viruses both as an immunomodulator and as an antiviral compound.

Adenine↗
PubMed1991

5-HT2 receptor antagonism in dysthymic disorder: a double-blind placebo-controlled study with ritanserin.

Thirty patients suffering from dysthymic disorder participated in a 6-week double-blind trial comparing ritanserin 10 mg and placebo. After a single-blind placebo wash-out period of one week, the test medication was administered during 5 weeks on a double-blind basis. Twenty-three patients completed the study. At the end of the trial, ritanserin was significantly superior to placebo in its effect as manifested on the 19-item Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety and the State Trait Anxiety Inventory X-1 and X-2. At the end of the study, the therapeutic effect was rated marked or moderate in 75% of the ritanserin-treated patients, but only in 18% of the controls. These data are consistent with the hypothesis of serotonin abnormalities in dysthymic disorder and suggest a therapeutic role of 5-HT2 antagonists. Ritanserin treatment was very well tolerated; no serious adverse experiences were reported.

Adult↗
PubMed1991

Monoclonal antibodies against protease inhibitors: the case of the bovine pancreatic trypsin inhibitor.

A monoclonal antibody (MoAb) directed against bovine basic pancreatic trypsin inhibitor (BPTI or aprotinin), a small protein made up by 58 aminoacids, has been produced. Mice were immunized with the native form of the protein and gave low antibody response. After somatic hybridization of spleen cells from immunized mice, few clones secreting antibodies against BPTI have been found and just two of them were stable. Both secreted IgM. One (ICI) produces a monoclonal antibody which binds to BPTI with an equilibrium dissociation constant, Kd, of 6.1 x 10(-7) M at pH 7.4. Competition experiments demonstrated that ICI recognizes an epitope close to the reactive site of BPTI. Furthermore, Kd of ICI with an isoinhibitor similar to BPTI (S.I. II) but with few differences at the active site is higher, confirming specificity of binding.

Animals↗
PubMed1991

Antibodies against small molecules.

Compounds with low molecular weight (haptens) are not usually immunogenic. Thus, an hapten should be conjugated with a carrier protein therefore immunizing an animal, in order to induce a strong immune response and in turn obtain large amount of antibodies. Suitable macromolecules are usually albumins, thyroglobulins, haemocyanins and polylysine. The production of specific antibodies against haptens is important both for assays of hormones and drugs in biological fluids or for therapeutic applications in tumour therapy. Approaches in choice of both carrier protein and conjugation methods will be described.

Animals↗
PubMed1990

Growth inhibition of Friend erythroleukaemia cell tumours in vivo by a synthetic analogue of prostaglandin A: an action independent of natural killer-activity.

Prostaglandins of the A series (PGAs) have been previously shown to inhibit the growth and to stimulate the differentiation of Friend erythroleukaemic cells (FLC) in vitro. In the present report we analysed the effect of PGA treatment in vitro on FLC tumorigenicity, and in vivo on FLC proliferation and on natural killer (NK) activity. PGA1 pretreatment of FLC in vitro for 5 days before inoculation into syngeneic mice slightly delayed tumour appearance, but did not significantly alter the pattern of tumour growth or mice survival, indicating that PGA1, at least in the conditions studied, did not affect FLC tumorigenicity. Daily treatment of mice with a long-acting synthetic analogue of PGA2 (16, 16 dimethyl-PGA2-methyl ester, di-M-PGA2) delayed tumour appearance, inhibited tumour growth, as measured by tumour weight and diameter, and increased the median mice survival time by 15-35%, depending on the schedule of treatment. Daily treatment with di-M-PGA2 strongly suppressed NK activity in normal mice but had no significant effect in tumour-bearing immunodepressed mice. PGA treatment of effector or target cells in vitro, or PGA added during the NK assay, had no effect on NK activity. We suggest that the chemotherapeutic effect of PGA is due to a direct action on tumour cell replication rather than to a stimulation of the host NK activity.

Animals↗
PubMed1990

5-HT2 antagonist ritanserin in neuroleptic-induced parkinsonism: a double-blind comparison with orphenadrine and placebo.

Several studies support the hypothesis of 5-HT (serotonin) involvement in the physiopathology of the extrapyramidal system. Ritanserin is a new compound with a high, selective, and long-lasting binding affinity for 5-HT2 receptors. A therapeutic effect of ritanserin has been reported in Parkinson's tremor and L-Dopa-induced dyskinesias but no effect was seen in essential tremor. In this double-blind comparative study with orphenadrine (150 mg daily p.o.) and placebo, ritanserin (30 mg daily p.o.) was administered to 36 schizophrenic outpatients who were being treated with neuroleptic drugs and who had parkinsonism. For a period of 3 weeks, the treatment was added to the antipsychotic therapy after a 7-day washout from previous antiparkinson medication. Psychopathology was rated weekly by the Brief Psychiatric Rating Scale and showed no significant changes during the trial. The Mindham Rating Scale was used to assess symptoms of parkinsonism; at week 3, ritanserin was superior to orphenadrine (p less than 0.03) and to placebo (p less than 0.01). The results confirm previous observations of the therapeutic efficacy of ritanserin on neuroleptic-induced parkinsonism, and support the hypothesis that serotonin influences extrapyramidal physiopathology.

Adolescent↗
PubMed1990

[Circadian rhythm of spontaneous ventricular arrhythmias in elderly patients with myocardial ischemia at low risk for sudden death].

In 26 patients (65-80 yr) with low risk of sudden death, the circadian rhythm of spontaneous ventricular arrhythmias was analyzed, throughout 72 h, by the Holter monitoring method. The prolonged ECG monitoring is indispensable to evaluate the real necessity of an antiarrhythmic therapy and to establish the therapeutic approach. Premature ventricular complexes (PVC): isolated, couplets and runs of ventricular tachycardia have been considered. The isolated PVC showed uniform distribution throughout 24h, with higher frequency/hour ratio (f/h) in females. Couplets and runs showed circadian diurnal distribution with higher f/h ratio in smokers and males. After analysis of the results, the patients were additionally subdivided into smokers and non-smokers. Since smokers showed a diurnal distribution of all kinds of arrhythmias, antiarrhythmic drugs whose pharmacological peak corresponds to the distribution peaks of arrhythmias were proposed. Non-smokers could be divided into two groups: a) patients with isolated extrasystoles which did not show a circadian rhythm of arrhythmias and who must be treated with retard-drugs, which give protection throughout 24h; b) patients with runs or couplets of PVC showing a circadian rhythm of arrhythmias and who must be treated with drugs whose pharmacological peak corresponds to the distribution peaks of arrhythmias.

Aged↗
PubMed1990

Suppressor cells induced by influenza virus inhibit interleukin-2 production in mice.

PR8 virus depressed interleukin-2 (IL-2) and natural killer (NK) cell activity in BALB/c infected mice. IL-2 production was not dependent on (i) a decreased number of T cells or (ii) a primary defect in IL-1 production, but on a T-suppressor cell subpopulation. In fact, when T suppressor cells were removed from infected spleen cells, we observed normal levels of IL-2 activity.

Animals↗
PubMed1989

A simple method for increasing hapten immunogenicity by a specific structural modification of the carrier.

A simple procedure to bind haptens, drugs or peptides selectively through their amino or carboxylic group to a spacer arm modified non-immunogenic polypeptide is described. Gelatin, a well known non-immunogenic carrier, was modified by blocking its amino groups. Spacer arms with primary amino groups such as beta-alanine or ethylenediamine were conjugated to this protein by carbodiimide resulting in spacer modified gelatin. These modified polypeptides were tested for their ability to selectively bind haptens through their amino or carboxylic groups. Three probes were used and the results obtained confirm the hypothesis. Three conjugates obtained were further used to induce an immune response in mice. Enhancement of the immunogenicity of these spacer-arm supported haptens was observed. Overall, this study provides a rational approach to the production of well defined antigens using a simple conjugation technique.

Acetylation↗
PubMed1989

Production and characterization of monoclonal antibodies against bovine pancreatic trypsin inhibitor.

Two monoclonal antibodies (MAbs) have been produced, without the use of a supporting carrier, against bovine basic pancreatic trypsin inhibitor (BPTI or aprotinin), a mini-protein composed of 58 amino acids. Both MAbs obtained were found to be IgM. One of them was purified and further characterized. This MAb (ICI) binds to the immunogen with an association constant of 1.6 X 10(6)M-1 at pH 7.4. Competition experiments with trypsin or inactivated trypsin demonstrate that ICI MAb interacts with BPTI at, or near, the proteinase-binding site. ICI MAb binds, with a much lower association constant (approximately 200M-1), to an isoinhibitor (spleen inhibitor II) which differs from BPTI in seven amino-acids; three of these substitutions are at the active site, in the contact area with the proteinase.

Animals↗
PubMed1989

Ritanserin versus lorazepam: a double-blind, cross-over study of reaction times in healthy volunteers.

Ritanserin, a benzydrilen-piperidine derivative, with a potent, selective and long-lasting antagonist activity on serotonin type 2 receptors, has shown anxyolitic properties and a lesser sedative profile than benzodiazepines. Ritanserin and lorazepam at therapeutical doses, were compared in eight healthy volunteers in a double-blind, cross-over study in order to detect possible different impairments of performances. Before and during the treatment, all subjects were daily submitted to a test of rapidity and regularity of response to acoustic and visual stimuli by means of an electronic device. A visual analogue scale for the self-assessment of the drowsiness degree was also administered. Ritanserin did not modify reaction times, while lorazepam significantly prolonged them. The analysis of data within treatments significantly favoured ritanserin, while between treatments there was only a trend in favour of ritanserin. The analogical scale for concentration showed a significant reduction with lorazepam, whereas for drowsiness no alteration occurred with either drug.

Acoustic Stimulation↗
PubMed1989

[Determination of the range of physiologic variation of the electrical axes using P, QRS, and T waves in pregnancy].

Since functional overload in pregnancy frequently induces the appearance of symptoms that could arouse suspicion of myocardiopathy, it is important to analyse and characterize all electrocardiographic modifications during a healthy subject's pregnancy. Variations of the mean electrical axis (A) of P, QRS and T waves were evaluated in 52 healthy volunteers, 17-37 years, during pregnancy. The A values were measured, in the frontal plane, at the end of both I and III quarter of pregnancy, using a method of scalar determination. The As in I and III quarters was compared with those observed in the post-partum (at 5th day) and statistical evaluations were performed (Student t-test for paired observations). In the I quarter the mean A was 40 +/- 3 degrees for P, 40 +/- 16 degrees for QRS and 32.5 +/- 9 degrees for T wave, whereas in the III quarter the mean A changed to 37 +/- 2 degrees for P, 34 +/- 18 degrees for QRS and 31 +/- 9 degrees for T. During pregnancy, all mean As significantly diverted to the left side, AP about 3 degrees, AQRS about 6 degrees and AT about 1.5 degrees. These results were also confirmed by analysis of A frequency distribution histograms. In the post-partum (5th day) the A resumed basal values (I quarter's values). These results show: i) the physiological range of AP, AQRS and AT, during pregnancy; ii) left deviation of all three As at the end of III quarter. It is possible to conclude that variation over this range, particularly for QRS, could give evidence of the onset of cardiopathy.

Adolescent↗
PubMed1988

Production and characterization of monoclonal antibodies against DNA single ring diamines adducts.

The synthetic conjugate of the genotoxic compound 2,4 diaminotoluene (2,4 DAT) with gelatin (2,4 DAT-GEL) was employed to elicit specific antibodies directed against a restricted class of aromatic diamines. Using this immunogen, mouse monoclonal antibodies (MAbs) have been produced. These MAbs have been characterized and used in ELISA to detect 2,4 DAT covalently linked to biopolymers. The MAbs could bind to different synthetic 2,4 DAT-biopolymer adducts as well as to DNA from rats treated in vivo with the aromatic diamine, but they did not react with gelatin or biopolymers alone. The use of these MAbs has been investigated in order to develop a highly sensitive test to detect adducts of this genotoxic compound with nuclear DNA.

Animals↗
PubMed1987

Effect of the 5HT2 antagonist ritanserin on food intake and on 5HT-induced anorexia in the rat.

The present study investigated the effect on the rat's eating behavior of the new selective 5HT2 antagonist ritanserin. The results obtained indicate that: single subcutaneous (SC) injection of ritanserin, at doses between 0.1 and 1 mg/kg b.wt., neither elicits food intake in sated rats, nor increases the intake induced by food deprivation; subchronic SC treatment (15 days) with 0.1 mg/kg does not increase food intake nor body weight gain; subchronic SC treatment with high doses, 1 or 10 mg/kg, produces small and transient increases in food intake without affecting body weight gain. When ritanserin was tested for its ability to block the anorectic effect of exogenous 5HT, it inhibited the effect of intraperitoneal (IP) 5HT, but proved to be completely inactive versus the effect of 5HT injected into the hypothalamic paraventricular nucleus, which is highly sensitive to this effect of 5HT. This last finding suggests that the anorectic action of central endogenous 5HT is also not blocked by ritanserin, thus proposing a reasonable explanation for the absence of orexigenic effect following its administration. Moreover, it suggests that in rats the hypothalamic receptors mediating the effect of 5HT on eating behavior are different from the 5HT2 of the frontal cortex which have been shown to be completely blocked by ritanserin under the experimental conditions employed in our study.

Animals↗
PubMed1987

Ritanserin, a serotonin-S2 receptor antagonist, does not prevent 5-hydroxytryptophan-induced beta-EP, beta-LPH and cortisol secretion.

Ritanserin, a new serotonin antagonist selective upon S2 receptor subclass is available. Thus, in order to better define the positive control of serotoninergic pathway on proopiomelanocortin (POMC)-related peptide release, a group of 7 healthy male volunteers has been submitted to a 5-hydroxytryptophane (5-OH-TP) test (200 mg p.o.) before and after 4 days Ritanserin pretreatment. Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol levels were measured hourly for 4 h after each 5-OH-TP loading. Hormonal levels were measured by specific RIAs on extracted (cortisol) and chromatographed (beta-EP and beta-LPH) plasma samples. Basal plasma concentrations of the three hormones were unchanged by Ritanserin pretreatment. Similarly, the integrated areas of beta-LPH, beta-EP and cortisol release in response to 5-OH-TP remained unaffected by the receptor blockade. These data confirm that serotonin-acting drugs are able to stimulate POMC-related peptide release and indicate that such interaction is not mediated through S2 receptor subclass.

5-Hydroxytryptophan↗
PubMed1987

Combined effects of immunity and antitumor drugs against cancer. II. In vitro studies with cis-diamminedichloroplatinum in a human leukemia system.

Human K562 leukemic cells were exposed in vitro to cis-diamminedichloroplatinum (DDP) followed by addition of intact or irradiated mononuclear cells (MNC) obtained from peripheral blood of normal donors. tumor inhibition provoked by DDP was significantly enhanced by normal MNC, but not by irradiated cells at the effector: leukemic cell ratio of 2:1. In contrast MNC alone did not show appreciable effects on K562 cells. The NK activity of MNC was also inhibited by exposure to gamma rays. The combined effects of DDP + MNC do not appear to be due to increased susceptibility of DDP-pretreated K562 cells to NK-mediated cytolysis. Actually leukemic cells treated with 10 micrograms/ml of DDP and cultured for 48 h at 37 degrees C, showed decline of susceptibility to the cytotoxic effects of MNC. These studies suggest that natural immunity could be of potential value in the clinical use of DDP.

Cell Division↗