Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships.

BACKGROUND: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors. OBJECTIVES: Evaluate retrospectively the efficacy of a regular and proactive follow-up of NF1 patients to early diagnose abdominal tumors and report their mutations. METHODS: Cohort study performed between 2010 and 2020, with 43 NF1 adult patients followed at our Dermatology department. RESULTS: Eight abdominal tumors were diagnosed in six patients, meaning that 14% of the followed patients developed an abdominal tumor. Five patients (83%) were asymptomatic. Five (83.3%) had a family history of NF1 with abdominal tumors (patients 1,2 and 3,4,5 were relatives). CONCLUSIONS: Although currently gastrointestinal routine screening investigations for asymptomatic patients are not recommended in the guidelines, the family aggregation in our series suggests it should be considered a close follow-up of the relatives of a patient with an NF1-related abdominal tumor. Also, for the first time, two mutations [c.2041C > T (p.Arg681Ter) and c.4537C > T (p.Arg1513*)] have been associated with family aggregation of abdominal tumors in NF1 patients.

[Study of lipids (cholesterol, triglycerides and phospholipids), plasma lipoproteins (HDL-cholesterol) and apoproteins (apo A and apo B in patients with acute myocardial infarction]. / Estudio de lípidos (colesterol, triglicéridos y fosfolípidos), lipoproteínas plasmáticas (HDL-colesterol) y apoproteínas (apo A y apo B) en pacientes con infarto agudo de miocardio.

Several lipid parameters were evaluated in 88 patients with acute myocardial infarction (AMI). A reduction in cholesterol and phospholipid level was observed, with minimal values between the days 10-20, followed by a subsequent increase. Triglycerides increased after 12-14 hours, with a maximal value after 20-30 days. Cholesterol bound to high-density lipoproteins (HDL-cholesterol) decreased after 24 hours, with a minimal value after 20-30 days. Apoprotein A decreased from the initial measurement until days 20-30. The initial lipid profile (indicating the risk of coronary artery disease) was constituted by high cholesterol (particularly in males below 60 years), high triglyceride and low HDL-cholesterol levels. The latter finding was more marked and characteristic in the overall group of evaluated patients. All values were compared with a control group of 24 healthy persons. Relevant data for prognosis included the following: males above 60 years had a greater reduction in cholesterol and apoprotein A during AMI; the males who died had lower apoprotein A levels than the survivors; females with higher haptoglobin levels also had higher apoprotein B levels. All these findings were statistically significant (p less than 0.01).

Action of persistent administration of a hapten with a reactive group (TNBS) and mono-or divalent conjugates of hapten to molecules without other reactive groups on anti-TNP-LPS response.

The intrinsic tolerization mechanisms of the B cell have been postulated either at the level of membrane receptor blockade, before the appearance of membrane receptors, or more intracellularly. For the first possibility a certain multivalence or epitope/hapten density of the antigen molecule is required. Tolerance has been induced by free haptens that possess a reactive group, but haptens lacking such a reactive group may not necessarily be tolerized. We studied the effect on a possible response to trinitrophenyl-lipopolysaccharide (TNP-LPS) by persistent stimulation of immature Swiss mice with: a free hapten containing a reactive group (trinitrobenzenesulfonic acid of TNBS), the low M.W. trinitrophenyl (TNP)-glycine conjugate, and dinitrophenyl (DNP)-polyethylene glycol conjugates; the M.W. of polyethylene glycol being 6,000, 20,000 and 35,000 respectively. Persistent injection of TNBS hapten profoundly tolerated the response to TNP-LPS, whereas the administration of TNP-glycine and DNP-polyethylene glycol conjugates not only fails to tolerate the response, but might stimulate it. Possible explanations for these results are discussed; the tolerogenicactivity of TNBS is ascribed to its binding to another receptor or membrane component, thus impairing "capping" formation by the specific receptor. Alternatively, by acting more intracellularly, TNBS may inhibit the B-cell maturation/differentiation. It would be interesting to find out whether the other conjugates, which are stimulant, could also be tolerated when inoculated for a very long period of time, as has been shown to happen with many antigens administered in immunogenic doses for several months.

[Parallelism between the kinetics of cross-reaction responses (anti-TNP and anti-DNP) and differences from the anti-LPS response when challenged with TNP-LPS immunization]. / Paralelismo de la cinética de las respuestas de reacción cruzada (anti-TNP y anti-DNP) y diferencias con la anti-LPS, frente a la inmunización con TNP-LPS.

The multi-functionality of a given antibody, even monoclonal antibody has recently been shown; this raises the possibility that the specificity of an antiserum be due to a population phenomena; i.e., the specificity would be the net result of the affinity of the various antibodies to the same hapten or antigenic determinant. We have shown in many reports, that prolonged and persistent immunization eventually leads to the exhaustion of the response, and this response ceases upon discontinuation of the antigen stimulation. We have therefore postulated the existence of an immunological equilibrium or antigen-dependent immunologic homeostasis, which can be set at different levels and this explains the formation or lack of formation of autoantibodies. This is why we considered it interesting to study the kinetics of the anti-TNP antibody response triggered by persistent and long-lasting immunization of rabbits with TNP-LPS; it was also interesting to study the antibody response to LPS (the latter being a component of the conjugate) and the antibody response to the TNP-cross-reacting DNP and MNP haptens. A group consisting of 6 big albino rabbits was persistently immunized with TNP-LPS (200 micrograms) 3 times per week for 14 weeks and, thereafter, with 2 mg 3 times per week for 26 weeks. Serum anti-TNP and anti-LPS antibodies were titrated respectively with the TNP-Srbc and LPS-Srbc conjugates. Anti-TNP antibodies were titrated before and after absorption of serum with the TNP-EH, DNP-EH and MNP-EH conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of IgG antibody formation by sublethal irradiation during persistently repeated immunization with Brucella abortas.

Whole-body irradiation with 600 rads 8 or 10 days after the beginning of persistently repeated Brucella abortus immunization in the rabbit produces little change in the response. By contrast, irradiation with the same dose 2, 4 or 6 days after the beginning of repeated immunization stimulates the IgG response. This effect is explained by a repopulation of antigen-sensitive cells from precursor cells to a higher level than that previous to irradiation. In order to explain IgG stimulation, three main possibilities are considered. a) a T cell-dependent mechanism, consequent on a higher radioresistance of T than of B cells, or on a faster and more extensive repopulation by T cells; b) another T cell-dependent mechanism due to a greater radiosensitivity of the suppressor or inhibitory T-cell subpopulation, with the result of a predominance in the T cell population that helps IgG formation; c) a mechanism depending on antigen presence during the repopulation of antigen-sensitive cells from the precursor cells, according to previously obtained data suggesting the necessity for the persistence of a certain level of antigen for IgG formation

Acute renal insufficiency in the rabbit by glycerol.

The appearance of an acute renal insufficiency in the rabbit, after glycerol injection (10, 13 or 15 ml/kg of a 50% solution) is investigated. After a 24 hours of intoxication, especially in the ten following days, cylinders, erythrocytes and renal cells appear in the urine sediment. Proteinuria appears after 24 hours and practically disappears after 72 h. Glucosuria persists from 24 hours to 6 days. Haemoglobinuria is intense after 24 and 48 hours and persists slightly about 6 days. Na, K and Cl elimination in urine diminishes clearly in all animals. Plasma K increases in non-surviving animals and does not change in those surviving. Plasma Na does not change in the dying ones, and decreases in those surviving. In non-surviving animals, pH, pCO2 and CO3H minus decrease sharply. In the surviving ones pCO2 decreases clearly after 24 hours, increasing afterwards slowly to normal values. pH increases, slightly during the first 48 hours, and then neatly during approximately 6 days. Standard CO2H minus does not change during the first 48 hours, increasing afterwards during 6 to 7 days. Histologically, the chief lesion is a vacuolar degeneration of the proximal tubule. The possible mechanisms of such alterations are discussed.