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Biomedical subjects

R Motta

Publications and source records attributed to R Motta.

At least 37 records · Page 2Linked to original sources
PubMed1992

Recombinant congenic strains of mice from B10.D2 and DBA/2: their contribution to behavior genetic research and application to audiogenic seizures.

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain ("donor" strain) on the genetic background of another strain ("background" strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.

Acoustic Stimulation↗
PubMed1992

Local haemofiltration with free radical scavenger treatment during revascularisation of severe muscular ischaemia induced in sheep limbs.

Many treatments have been proposed for the prevention of the revascularisation syndrome following embolectomy or thrombectomy in patients with severe ischaemia. These include the administration of diuretics, bicarbonate, buffer solutions, free radical scavengers, washing out the venous blood from the ischaemic leg, or systemic dialysis. The aim of our study was to investigate the effect of combining haemofiltration with a treatment using compound oxy-radical scavengers in order to prevent or to reduce the appearance of the revascularisation syndrome. The study was performed on 13 sheep. Eight animals underwent 4 h of aortic and vena cava occlusion using irrigation-occlusion catheters, followed by normal reperfusion (control group). Five sheep underwent the same period of ischaemia, followed by 1 h of local haemofiltration and re-oxygenation and 2 h of normal revascularisation. The priming solution for the ECC circuit consisted of 500 ml of 20% mannitol and 500 ml of 18/1000 HCO3- contained: superoxide dismutase (150,000 I.U.), methylprednisolone, 1 g, and heparin, 10,000 I.U. After the 3rd h of ischaemia, 2.1 g of acetate alpha-tocopherol (30 mg kg-1) were injected i.m. The treatment produced good protection against oxidative stress, shown by an increase in the glutathione ratio (GSH/GSSG), and reduced muscular damage, confirmed by a moderate increase in creatine phosphokinase (CPK) levels (significantly higher in the control group). Diuresis was significantly higher in the treated group, and the acid-basic and potassium balance returned to normal more rapidly. Our data suggest that this combined treatment could be effective in the prevention of the ischaemia-reperfusion syndrome.

Animals↗
PubMed1992

Lipid, lipoprotein, and apolipoprotein assessment during an 8-wk very-low-calorie diet.

The influence of a very-low-calorie diet (VLCD) on lipid pattern is controversial. To evaluate the long-term effect of semistarvation on lipid patterns, a group of severely obese patients [aged 37 +/- 12 y, body mass index (BMI) 40.0 +/- 0.9] underwent a VLCD for 8 wk. Total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), triglycerides (TGs), apolipoproteins A1 (apo A1) and B (apo B) were analyzed every week. TC (6.07 +/- 0.23 vs 5.53 +/- 0.25 mmol/L, P less than 0.0008), HDL-C (mmol/L 1.26 +/- 0.06 vs 1.04 +/- 0.05 mmol/L, P less than 0.0001), TGs (1.46 +/- 0.19 vs 1.06 +/- 0.10 mmol/L, P less than 0.0008), and apo A1 (1.57 +/- 0.06 vs 1.32 +/- 0.06 g/L, P less than 0.0002) decreased, whereas LDL-C and apo B showed a biphasic behavior: they significantly fell during the first 3 wk, but during the last weeks returned to their initial values.

Adult↗
PubMed1991

Myocardial metabolic and hemodynamic effects of a sustained intravenous infusion of nifedipine with and without metoprolol in patients with unstable angina.

We tested the usefulness of a sustained intravenous infusion of nifedipine and a combination of nifedipine and metoprolol in the early management of 14 patients with unstable angina pectoris. After a 24-hour run-in period, nifedipine was titrated in a stepwise fashion (mean dose 27 +/- 7 micrograms/min). After nifedipine treatment coronary blood flow increased from 150 +/- 66 to 183 +/- 74 ml/min (p less than 0.05), whereas double product, myocardial oxygen consumption, and both arterial and coronary sinus (nor)epinephrine levels were unchanged. Myocardial lactate uptake increased from 3.4 +/- 26.1 to 31.3 +/- 26.6 mumol/min (p less than 0.005) and free fatty acid uptake from 7.2 +/- 22.1 to 34.5 +/- 33.7 mumol/min (p less than 0.05). A small nonsignificant improvement in amino acid metabolism was observed. Metoprolol was added in seven patients and led to a decrease in double product (-2.2 +/- 1.6 x 10(3); p less than 0.01) and myocardial oxygen consumption (-3.2 +/- 3.8 ml/min; p less than 0.05). The lactate uptake/oxygen uptake ratio increased by 18% after metoprolol (p = NS). The number of episodes of chest pain decreased from 2.4 +/- 1.1/24 hours to 0.1 +/- 0.2 in the nifedipine group and from 2.9 +/- 1.1/24 hours to 0.3 +/- 0.5 in the nifedipine plus metoprolol group (both p less than 0.01). We conclude that in the acute phase of unstable angina, intravenous nifedipine can be carefully titrated to improve coronary blood flow and oxidative metabolism. The addition of metoprolol is also associated with a reduction in myocardial oxygen demand. This treatment results in significant hemodynamic stability.

Adult↗
PubMed1990

Graft-versus-host mortality induced by noncytolytic CD4+ T cell clones specific for non-H-2 antigens.

UNLABELLED: The relative contribution of individual non-H-2 Ag and of T cell subsets that initiate graft-vs-host reaction (GVHR) as well as the mechanism responsible for histopathologic lesions are still a matter of debate. To address these questions and to favor the selection of T cells primed in vivo against non-H-2 Ag important in GVHR we derived T cell clones from spleens of (DBA/2 x B10.D2)F1 (H-2d) mice developing this reaction after the graft of B10.D2 (H-2d) cells incompatible for numerous non-H-2 Ag plus Mlsa. The pattern of reactivity of eight selected clones against cells from different strains of mice including (BXD)RI strains indicated that one CD4+ clone is specific for Mlsa and seven additional clones (six CD4+ and one CD8+) are specific for four different non-H-2 Ag (Ag.I-IV) and proliferate in an H-2-restricted manner. The same series of experiments suggested that Ag.I and II are poorly polymorphic and allowed to propose the localisation of the genes controlling Ag.I (chromosome 1) and Ag.III (chromosome 4). All the clones show a triple (alpha, beta, gamma) mRNA transcript for TCR but at their surface they express the alpha/beta-heterodimer. The clone specific for Mlsa expresses V beta 6 and that specific for Ag.IV expresses V beta 8.1. Rapid mortality accompanied by clinical and histologic signs of severe GVHR was observed after administration of CD4+ clones (together with host-syngeneic bone marrow) derived early after grafting and specific for Ag.I and II but not after administration of: 1) CD8+ cytolytic clone derived early after grafting and specific for Ag.IV; 2) CD4+ clones derived late after grafting and specific for Ag.III; and 3) CD4+ clone specific for Mlsa. A clear correlation was established between the capacity of CD4+ clones to induce GVHR mortality, to mediate host-specific DTH and to release a high level of TNF. IN CONCLUSION: 1) the reaction against a single non-H-2 Ag is sufficient to provoke lethal GVHR; 2) the capacity to provoke GVHR mortality depends on antigenic specificity and functional properties of the responding clones; 3) the inflammatory process mediated by CD4+ clones may play a major role whereas the specific CD8+ T cell-mediated cytolytic activity is not necessarily lethal.

Animals↗
PubMed1990

Bioluminescent flow sensor for the determination of L-(+)-lactate.

The amount of L-lactate in biological fluids (serum, plasma and cerebrospinal fluid) was determined by monitoring the reduced form of nicotinamide adenine dinucleotide (NADH) produced by immobilised lactate dehydrogenase (LDH), with bacterial bioluminescent enzymes immobilised on a separate nylon coil. The LDH catalysed the reaction of L-lactate with NAD; this reaction took place in a nylon coil that preceded the coil for the bioluminescent detection. The co-immobilisation of alanine aminotransferase (ALT) with LDH improved the lactate transformation by 117-183%. The response was linear from 0.1 to 50 micron mol l(-1) at 25 degrees C for the LDH - ALT reactor. The intra- and inter-assay coefficients of variation were less than 5% and the recoveries ranged from 93 to 106%. The results agreed well with those obtained with a spectrophotometric method and with the normal reference values.

Alanine Transaminase↗
PubMed1990

Therapeutic techniques vs therapeutic relationships in child behavior therapy.

The parents of 56 children who had received behavior therapy rated a number of variables, including the degree to which they viewed the therapeutic relationship versus the specific techniques used in treatment as important, the extent to which the child improved in therapy, and the child's present functioning. Therapists also provided ratings of clinical improvement. Even though parents gave the highest ratings for the importance of the relationship in therapy, the correlation between technique and clinical outcome was statistically significant while the correlations between the relationship and outcome was not. These statistical associations also held when therapists rated improvement. Also, therapists saw greater improvement in children than did the parents. Over-all, the results support the view that the relationship and techniques are interwoven and are both perceived as important factors in treatment.

Adolescent↗
PubMed1990

The influence of the athymic mutation nude on the components of the circadian rhythm of activity in mice.

The mutation known as nude brings about the lack of a thymus gland in mice. This immunodeficiency akes it possible to graft normally unaccepted, human cancerous tumors onto the mouse. Consequently, this animal is frequently used as a model for evaluating anti-cancer therapies. The effect of this mutation on biological rhythms constitutes a necessary step before using this model for cancer chronotherapy research. We evaluated the circadian and ultradian components of the rest-activity cycle in the following strains of mice: C57BL/6 with homozygous nu/nu, heterozygous nu/+, thymectomised +/+, and sham-operated +/+. The amount of activity was reduced in nu/nu as compared to the other groups. Nonetheless, neither the nude mutation nor thymectomy yielded any notable change in the circadian rhythm of activity.

Activity Cycles↗
PubMed1989

Peripheral venous nutrition in surgical patients: techniques, indications and results.

Peripheral venous nutrition (PVN) has been proposed to avoid complications resulting from central venous catheterization in surgical patients. Using lipid emulsions 3 standard diets (with final osmolarity not higher than 900 mOsm/1, non-protein calories from 1675 to 2177, electrolytes 110 mEq, Cal/N ratio from 130/1 to 170/1) were worked out. They are suitable for total nutrition of non-hypercatabolic patients and for nutritional postoperative maintenance of patients undergoing major digestive tract surgery. The three diets were tested in 118 patients. Frequency and type of phlebitis and the nutritional status before and after treatment were evaluated in patients submitted to PVN and in 2 groups of 10 patients who received S-D5W infusions and Protein Sparing Nutrition (N = 12.8 g, total Cal. = 690, electrolytes = 110 mEq, osmolarity = 493 mOsm/l, pH = 7) in the postoperative period. Frequency of phlebitis was significantly lower in PVN patients than in control groups. 15 day treatment did not increase the frequency of phlebitis. In medium-term treated patients the mean daily nitrogen balance was always positive. Perioperative PVN achieved a statistically significant reduction of nitrogen losses with respect to PSN and S-DSW infusion.

Adult↗
PubMed1988

Neonatal thymus provides all the information required for tolerance induction against all the non-thymic organ-specific minor histocompatibility antigens.

Using our original "in vivo MLR" technique, we demonstrated that B10.D2 cells grafted into irradiated (DBA/2 x B10.D2)F1 mice (H-2d/H-2d) were stimulated to divide by the whole non-H-2 minor histocompatibility antigens (MiHA) of the DBA/2 background in each organ where these MiHA are expressed. When B10.D2 cells were grafted into N7 mice (generation descending from six successive backcrosses with B10.D2 after an initial cross DBA/2 x B10.D2) which had kept 1/64 of the DBA/2 genetic background, a lack of correlation between the levels of stimulation in the different organs of the same mouse was demonstrated. We established that the number of expressed MiHA lies between 7 and more than 100, depending on the organ, and that the organ specificity is a feature of the expression of these MiHA. Furthermore, using a different technique, we demonstrated that B10.D2 T cells can acquire a specific tolerance state towards the whole DBA/2 antigen background throughout maturation and differentiation in a fully syngeneic environment with the exception of a neonate-(DBA/2 x B10.D2)F1 grafted thymus. We concluded, therefore, that all information corresponding to the adult- and organ-specific MiHA is available in the neonatal thymus. Three working hypotheses are proposed to reconcile the two lines of results.

Animals↗
PubMed1988

Mathematical analysis of haemopoietic grafted cell renewal and migration through the allogeneic or syngeneic mouse host.

A mathematical analysis of results from kinetic studies of 125-iododeoxyuridine uptake and loss in almost all the lymphoid and non-lymphoid organs of mice is described. Applied to data gathered from a graft-versus-host reaction experiment, this analysis affords quantitative precision on the differential effects of organ alloantigens on the proliferating grafted cells. It is shown that, depending on the organ and the post-graft period, cell growth can be ascribed to alloantigen-driven cell renewal or to alloantigen-driven trapping or sequestration. Possible applications of the present approach in graft rejection monitoring are discussed.

Animals↗
PubMed1988

Endocrine involvement in minor (non-H-2) graft versus host reaction in mice: dissociated effect on corticosterone and aldosterone plasma levels.

The graft vs. host reaction (GVHR) induced across a non-H-2 histocompatibility antigen barrier was shown to be a multiorgan disease with a strict time-dependent pattern of functional alterations. The present study was undertaken to examine the effects of the GVHR on corticosterone, aldosterone, corticotropin (ACTH), Na+, and K+ plasma concentrations in mice. GVHR was induced in irradiated (DBA/2 X B10.D2)F1 mice by transplantation of B10.D2 hemopoietic cells. Controls were untreated F1 mice and irradiated syngeneic (F1) cell-grafted F1 mice. Nonimmunological stimuli transiently increased ACTH and corticosterone plasma levels during the first 5 days, although the early ACTH peak was markedly reduced in GVHR mice. Circulating corticosterone levels returned to normal values thereafter in controls. ACTH returned to basal levels in all mice, even in GVHR mice in spite of their persistent high corticosteronism. The enhancing effect of GVHR on plasma aldosterone concentrations was delayed until day 30 after the cell graft. Results suggest 1) a dissociated effect of GVHR on mineralocorticoid and glucocorticoid metabolism and 2) either an alteration of adrenal sensitivity to ACTH in GVHR mice or a possible mimicking of some neuroendocrine activities by the lymphocytes responsible for the onset of the disease.

Adrenocorticotropic Hormone↗
PubMed1988

Non-lymphoid thymic components tolerize T cell precursors to all the minor histocompatibility antigens of the thymus-donor strain.

Two months after adult-thymectomy, male B10.D2 mice were irradiated (6.5 Gy), injected with B10.D2 bone marrow cells and grafted with untreated neonate (DBA/2 X B10.D2)F1 (H-2d/H-2d) thymus [D2.F1]. Control (D2.D2) mice were implanted with B10.D2 thymus. T cells from [D2.F1] mice revealed to be fully immunocompetent while being tolerant to the minor histocompatibility antigens (MiHA) differing between DBA/2 and B10.D2 strains by in vitro and in vivo assays. Their transplantation into F1 irradiated (8.5 Gy) recipients did not induce any clinical sign of graft-versus-host reaction (GVHR) whereas this reaction is lethal when the transplantation is realized with normal B10.D2 or [D2.D2] hemopoietic cells. (D2.F1) transplanted cells were not stimulated to divide in non-lymphoid organs of the F1 hosts while this stimulation is a characteristic feature of the early period of the GVHR. Tolerance was due neither to detectable chimerism of the thymus-grafted host nor to active suppression. It is concluded that the thymus plays a sufficient and essential role for the proper acquisition of T cell immunocompetence and tolerance to all the minor histocompatibility antigens of the thymus-donor strain. Since we have previously reported that MiHA are numerous and highly organ-specific, the expression or the presence of all these MiHA in the non-lymphoid components of the thymus is questioned.

Animals↗
PubMed1987

Implications of disaggregation procedures on biological representation of human solid tumours.

This study was designed to define some biological aspects of cell suspensions, obtained by mechanical or enzymatic disaggregations, and to verify whether single cell suspensions are representative of original solid tumours. The study was performed on a series of 25 human solid tumours including breast carcinoma, ovarian carcinoma and malignant melanoma. A higher cell viability and a loss of aneuploid subpopulations, or a lower fraction of aneuploid cells, were observed in enzymatically-released samples than in samples obtained by the mechanical procedure. Moreover, the proliferative activity, which was generally similar for the cell suspensions obtained by the two disaggregation procedures, was always markedly lower in the cell suspensions than in solid samples from the same tumour. In conclusion, the results from this study indicate that many changes, such as selective release of cell populations from the tumour matrix, damage and destruction of aneuploid and proliferating cells can be induced to various extents by different disaggregation procedures.

Breast Neoplasms↗
PubMed1987

Endocrine involvement in minor (non-H-2) graft-versus-host reaction in mice. Early and primary thyroid failure.

A minor (non-H-2) graft-vs.-host reaction (GVHR) was induced in adult irradiated (DBA/2 X B10.D2)F1 mice by hematopoietic parental B10.D2 cell grafts. Syngeneic (F1) cell transplantation was performed as control. In one set of experiments T4 plasma level (enzyme linked immunosorbent assay) was systematically followed up in individual GVHR and control mice. Compared to the control, GVHR triggered off a significant and sustained decrease of T4 plasma level. In another set of experiments, TSH plasma levels (RIA) were measured in killed animals. GVHR induced an early elevation of plasma TSH. In a third set of experiments, mice undergoing GVHR received daily injections of L-T4 (0.03, 0.15, or 0.3 microgram/mouse). Compared to the control (saline injected) GVHR mice, T4 supply did not improve GVHR state. No positive effect of the high dose and rather a negative effect of both lower doses especially on glucose plasma concentration, were observed. All these data suggest that thyroid gland is primarily and very early involved in the onset of the GVH disease.

Animals↗