Showing papers by "University of Milan published in 1975"

Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs

Abstract: Summary. Adrenaline, nicotinic acid (NA), vasopressin (LVP) and other drugs affecting vascular motility are known to increase plasminogen activator (PA) and factor-VIII plasma levels in man. To evaluate the hypothesis that NA, LVP and adrenaline release PA from the endothelial cells of the vessel wall through their common effect on vascular motility, PA has been characterized by means of a histochemical technique on vein biopsies obtained from human volunteers after infusion of the compounds. Furthermore, the effect of single and repeated administration has been compared in order to investigate whether the pattern of PA and factor-VIII variations in plasma is similar with the three drugs. There was no major difference in the PA content of the veins following the marked and sustained increase of the corresponding plasma activities. A simple explanation is that the intensity and duration of the stimulus may not be sufficient to deplete the large stores of the vessel walls. The magnitude, time course and duration of the plasmatic response after single and repeated infusions was on the whole different and peculiar for each drug. A derivative of LVP which is free of vasoactive actions was more effective than LVP in inducing the responses, which could also be elicited in two anephric subjects. These findings suggest that vasoactivity is unlikely to provide the clue to a common pathway for the fibrinolysis and coagulation response after the compounds, and support the existence of different specific receptors.

Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold.

Abstract: A train of gated stimuli scanning the entire vulnerable period was delivered to the right anterior or left posterior ventricular surface to study the ventricular fibrillation threshold in anesthetized and vagotomized dogs. Heart rate was held constant by atrial pacing. Measurements were obtained in control conditions and after surgical removal of one stellate ganglion. To avoid the shortcomings associated with an irreversible procedure like stellectomy, control fibrillation threshold measurements were also alternated with determinations during reversible blockade by cooling of one stellate ganglion. The results were similar with both techniques. In nine animals, ablation or cooling of the left stellate ganglion increased ventricular fibrillation threshold by 72 ± 35 (mean ± standard deviation) percent compared with control values (P These results suggest that right and left cardiac sympathetic nerves may have different and specific effects on cardiac excitability. They also contribute to the understanding of the pathogenesis of the long Q-T syndrome (characterized by episodes of ventricular fibrillation associated with increased sympathetic activity) and increase the rationale for left stellectomy as the specific treatment for this illness. Left stellectomy, by raising the ventricular fibrillation threshold, may also represent an alternative measure in patients at high risk of sudden death from ventricular arrhythmias resistant to medical therapy.

Left and right heart haemodynamics during spontaneous angina pectoris. Comparison between angina with ST segment depression and angina with ST segment elevation.

Abstract: The function of both right and left sides of the heart was studied during spontaneous attacks of angina pectoris at rest in 7 patients showing ST depression (type I) and 4 showing ST elevation (type II) during the attack. In none of the 44 type I attacks and 29 type II attacks which were recorded did circulatory changes; the latter were different in the two groups. Type I attacks showed: a) a brief fall in arterial pressure, accompanied by b) a rise of right atrial and pulmonary wedge pressures and c) a decrease of cardiac output, right and left stroke work, the mean rate of systolic ejection, and indirect left ventricular pre-ejection dP/dt. In the course of the attack a hypertensive phase followed, which was paralleled by an increase of heart rate, cardiac output, left and right stroke work, and mean systolic ejection rate, left dP/dt; right atrial pressure and wedge pressure remained raised. All of the circulatory functions started to revert towards the pre-attack levels coincident with the waning phase of the electrocardiographic alteration, the latter occurring either spontaneously or after nitroglycerin. Type II attacks for the entire duration of the electrocardiographic changes showed: a) a reduction of arterial pressure, cardiac output, right and left stroke work, mean systolic ejection rate, and left dP/dt, b) a rise of right atrial and wedge pressures, and c) quite small changes of heart rate. When the electrocardiogram started to revert to the pre-attack aspect, the cardiac function rapidly improved and, after a supernormal phase, returned to the basal levels in about 2 minutes. It is concluded: 1) that no circulatory factor interfering with the mechanical effort of the heart is responsible for eliciting spontaneous angina: 2) that in type I attacks right and left ventricular impairment occurs which recovers rapidly, possibly through a sympathetic compensation; 3) that in type II attachs dysfunction of both sides of the heart occurs and persists throughout the episode of electrocardiographic alteration; 4) that the dynamic impairment is probably more severe in type I than in type II angina.

Asymptomatic liver disease in haemophiliacs.

Abstract: The incidence of jaundice and of abnormal liver function tests has been assessed in 91 multitransfused patients with severe haemophilia A and B. Tests of hepatocyte function were within the normal range in the majority of patients. On the contrary, tests of biliary cell function, liver cell damage, and bromsulphthalein retention gave high rates of abnormal values, which tended to increase with age. Hepatitis B surface antigen was present in 8% and the corresponding antibody in 66% of the cases; 18% had a history of jaundice. All patients were asymptomatic and only a minority showed clinical signs of liver involvement. These data suggest that in haemophilacs repeated and prolonged contact with the agent(s) responsible for post-transfusion hepatitis may cause chronic liver damage not associated with overt illness.

Genetic variability of gametophyte growth rate in maize.

Abstract: In order to measure differences in the pollen growth rate of numerous lines of maize and to investigate the main features of their genetic control, gametophyte growth was studied in vitro and in vivo. In vitro pollen tube growth of twenty inbred lines and seven hybrids was measured; a remarkable variability was observed in the growth rate of the inbred lines examined: most lines were distinct, showing different levels of growth. Analysis of frequency distribution of pollen tube lengths for pairs of inbred lines and their F1′ s revealed greater variance among lengths of F1 pollen tubes, presumably indicating the segregation of genetic factors expressed in the gametophyte. Similar frequency distributions of tube lengths in pollen produced by two pairs of reciprocal hybrids virtually excluded the presence of a cytoplasmic component. In vivo competitive ability of pollen tubes was measured as the increase in relative fertilization frequency from apex to base of the ear. Mixtures were made using two types of genetically distinguishable pollen, and were applied to a female common parent. Nine pairs of inbred lines furnished the pollen for the mixtures. In all cases where the B14 line was involved, this pollen type fertilized nearly all the ovules, perhaps indicating the presence of a gametophytic factor. When other lines were compared, the ears contained mixtures of the two possible seed types, the relative proportions of which indicated the differential competitive abilities of the two pollen tube types. A comparison between in vitro and in vivo behavior was made for some genotypes. In vivo results generally agreed with in vitro results. The degree of the differences between lines however was changed, presumably because pollen-style or pollen-pollen interactions are absent in vitro. Differing growth patterns between lines were also revealed in vivo by direct observation of fluorescent pollen tubes within the silks, a finding which may be useful in further studies.

Acidification of the Medium Associated with Normal and Fusicoccin-Induced Seed Germination

Abstract: Fusicoccin, a toxin stimulating cell enlargement and inducing proton extrusion in various plant tissues, has been shown to replace kinetin, gibberellic acid and red light in breaking seed dormancy. It also removes the inhibitory effect of abscisic acid. The present data also show that the stimulating effect of fucicoccin on embryo growth of decoated radish (Raphanus sativus L.) and maize (Zea mays) seeds and on the development of maize embryos is accompanied by an early, significant acidification of the medium. Acidification of the medium is also observed when fusicoccin reverses the abscisic acid-induced inhibition of germination. These results support the hypothesis that the mode of action of fusicoccin in promoting germination involves, as in stimulation of cell enlargement, the activation at the cell membrane level of proton extrusion processes. The physiological significance of fusicoccin-induced release of protons at the onset of germination is discussed in comparison with the results concerning the mechanism of action of fusicoccin on cell enlargement in other plant materials.

Hereditary Giant Platelet Syndrome

Abstract: The platelets from two related patients with the hereditary giant platelet syndrome were examined. They were larger than normal but otherwise ultrastructurally normal; they contained increased storage pools of adenine nucleotides and heparin-neutralizing activity and took up serotonin at an increased rate. They aggregated normally with ADP and collagen but failed to aggregate with bovine factor VIII and Ristocetin. Some change in shape occurred with ADP, and the reduction in adenylate energy change after addition of ADP to platelet-rich plasma was smaller than normal. Platelet coagulant activities including contact product forming activity, intrinsic factor-Xa forming activity and platelet factor 3 activity were normal or increased, but collagen-induced coagulant activity was absent whether tested in washed platelet suspensions or platelet-rich plasma. Platelet washing experiments showed decreased binding of factors V and VIII to hereditary giant platelets and no detectable factor XI in washed platelet suspensions. It is concluded that (1) the hereditary giant platelets studied lacked a binding mechanism for factors, V, VIII and XI; (2) the normal development of collagen-induced coagulant activity apparently depends upon the binding of factor XI to the platelet membrane; and (3) the defective prothrombin consumption observed in these patients may have resulted from the failure of their platelets to bind factor XI.

Conservative neck dissection.

Abstract: The areolar tissue which fills the laterovisceral spaces of the neck is thought to be in close contact with the limiting muscle and the large vessels and nerves of the neck. The site of lymph nodes and lymphatic vessels in such tissue is not clearly defined. A more profound anatomical study shows that the areolar tissue contains the whole lymphatic system of the neck, limited by a series of aponeuroses. These are derived from the embryonal mesenchyme, surrounding muscles and vessels, giving origin to a series of compartments which are in continuity with each other. These compartments, which contain the lymphatic structures, may be entirely removed en bloc including their limiting aponeurotical membranes, as long as the latter are carefully stripped from the muscular and vascular structures. This technique of neck dissection originating with O. Suarez in Argentina, is as radical as any traditional neck dissection, providing that some technical details are respected and that the nodes are still mobile. By preserving many useful or necessary structures of the neck, which themselves are unrelated to the lymphatic spread of cancer, conservative neck dissection presents important functional and cosmetic advantages as compared with traditional neck dissection.

Molecular organization of rat prolactin granules: in vitro stability of intact and "membraneless" granules

Abstract: Studies carried out on a number of secretory cell systems suggest that the specific cytoplasmic granules in which the secretion products are stored before their release are complex organelles which can possess a distinct molecular organization. For instance, it has been reported that in some granules the segregated secretion products are organized into crystalline structures (1-3) or large intermolecular aggregates (4-8). It is likely that all phenomena of this type are favorable to the economy of the cell, in the sense that they reduce the energy required for storage of the secretion products. The prolactin (LTH) granules of the rat pituitary possess a number of morphological features which strongly suggest that the molecules(s) of their content might be arranged in a relatively stable structure. Thus, these granules are remarkably polymorphic in shape, and their membrane is usually separated from their content by a clear space. Furthermore, identifiable LTH granules devoid of their membrane are often seen in the pericapillary space, suggesting that upon discharge by exocytosis they are dissolved only slowly (9). However, no studies specifically concerned with the mechanisms of LTH storage have been reported so far. In order to obtain some information on this question, we have studied the behavior of isolated granule fractions incubated in vitro under a variety of carefully controlled experimental conditions.

Transcellular ion route in rabbit gallbladder. Electric properties of the epithelial cells.

Abstract: The intracellular potential in gallbladder epithelial cells is about −59 mV with respect to both mucosal and serosal media.

The Role Played by Elasticity in an Exercise Involving Movements of Small Amplitude

Abstract: In an exercise consisting of repetitive small jumps on both feet at a frequency of 116/min, the mechanical work performed and the O2 consumption at steady state were measured. Of the positive work performed in the jump only 40% appears to be due to the chemical transformations taking place in the contractile component of the muscle fibres; the remaining 60% appears to be due to the elastic energy accumulated in the elastic elements of the contracted stretched muscles of the lower limbs during the falling phase of the previous jump, when the body hits the ground.

Glucose-insulin metabolism in chronic schizophrenia

Abstract: Publisher Summary This chapter deals with possible connections between the schizophrenic syndrome and alterations of glucose-insulin metabolism. Data are obtained in 18 patients, 9 males and 9 females, aged 22-62 years, suffering from chronic schizophrenia of 5-29 years duration. The patients were treated with haloperidol for 30 days, 6 mg/day i.m. to a total dose of 180 mg. The chapter also examines 12 physically and mentally healthy controls, matched for age and sex. The results are indicative of the presence of chemical diabetes in a significantly high percentage of patients, as demonstrated by markedly elevated insulinemic and glycemic peak values, delayed insulinemic and glycemic peak values, and prolonged hyperglycemia and hyperinsulinemia. The response to exogenously administered insulin was normal rather than excessive. Haloperidol treatment did not modify these results. The biochemical data seem to correlate with the presence of specific psychopathological symptomatology, such as severe mental deterioration, apathy and withdrawal from reality.

Na+ and Cl- transepithelial routes in rabbit gallbladder: tracer analysis of the transports.

Abstract: The reported experiments demonstrate that in rabbit gallbladder epithelium: a) The mucosa-cell Na+ and Cl− influxes (45 sec long) are reduced in Cl−-free and Na+-free bathing solutions respectively; transconcentration effects are observed. b) Cell Cl− labelling through the luminal membrane, with36Cl− (1 hr incubation), is nearly abolished if a Na+-free bathing solution is used; but cell Na+ labelling with22Na+ in the lumen (1 hr incubation) does not change if a Cl−-free bathing solution is employed. c) Cell Na+ and Cl− labelling through the basolateral membrane (1 hr incubation) is negligible; some Cl− labelling is obtained only when the intracellular electrical potential is artificially reduced. d) SO42− is found to abolish net water transport, to cross the epithelium, but not to enter the cell.

A mutation causing proline requirement in Zea mays

Abstract: A conditional seedling lethal, monogenic recessive, endosperm mutant is described. Phenotypic can be accomplished when embryos are cultured in vitro on media supplemented with proline. The efficiency of the repair is proportional to the concentration of proline in the medium. Normal growth is resumed at a dose of 160 mg/l. All the data collected are most easily interpreted by assuming that the mutant, symbolized pro has a genetic block in the biosynthetic route leading to proline.This is probably the first case of a strict genetic requirement for an amino acid to be reported in Zea mays. The possible reasons for the difficulties encountered in isolating obligate auxotrophs in higher plants are briefly reviewed.

Stress-induced and sympathetically-mediated electrocardiographic and circulatory variations in the primary hyperkinetic heart syndrome.

Abstract: As shown by the inotropic changes, the sympathetic discharge on the heart, is selectively enhanced by mental stimuli, and inhibited by pain in the primary hyperkinetic heart syndrome. In the steady state the electrocardiogram shows flat, diphasic, or 'tucked' T waves. Mental stimulation or isoproterenol, and, respectively, pain or beta blockade induce changes of the repolarization phase divergent from steady state. The former causes ST depression and deep T-wave inversion and the latter fully normalizes the repolarization phase. It is concluded that the electrical activity of the heart is directly influenced by the adrenergic drive in this disorder, and that different stressful factors can alter the repolarization phase in opposite ways in relation to the influence of the stimulus on the cardiac sympathetic tone.

Calcium and pancreatic secretion-dynamics of subcellular calcium pools in resting and stimulated acinar cells

Abstract: 1 Pulse-chase experiments were carried out on pancreatic tissue lobules incubated in vitro, with 45Ca as the tracer, in order to shed some light on the functional significance of the calcium pools associated with the various cell organelles of the acinar cell, especially in relation to stimulus-secretion coupling. 2 The kinetics of tracer uptake and release which were observed in the intact lobules suggest the existence of a number of intracellular pools, whose rate of exchange is slower than that across teh plasmalemma. 3 The various subcellular fractions accumulate the tracer in different amounts: some (rough microsomes and postmicrosomal supernatant) showed little radioactivity and some (smooth microsomes and zymogen granule membranes) were heavily labelled; mitochondria and zymogen granules showed intermediate values. 4 The fractions are heterogeneous also in relation to the time course of uptake and release of the tracer: in rough and smooth microsomes and, especially, in the postmicrosomal supernatant both rates were fast; zymogen granules and zymogen granule membranes showed slow rates of uptake and little release during chase; intermediate rates were found in mitochondria. 5 In agreement with previous findings we observed that in 45Ca preloaded lobules, stimulation of secretion (brought about by the secretagogue polypeptide caerulein) results in an increase of the tracer release which seems to be due primarily to the rise of the intracellular concentration of free Ca2+ and to the consequent increase of the transmembrane Ca2+ efflux. Among the cell fractions isolated from stimulated lobules only the mitochondria exhibited a significantly lower 45Ca level relative to the unstimulated controls. 6 It is concluded that, of the organelle-bound calcium pools, that associated with the mitochondria might be involved in the regulation of the calcium-dependent functions, including stimulus-secretion coupling; the calcium associated with the zymogen granule content probably has a role in the architecture of the organelle and in the functionality of the pancreatic juice, while the calcium bound to the membrane of the granules might be concerned with the regulation of its permeability properties.

Identification of the high and low affinity CO2-binding sites of human haemoglobin.

Abstract: THE unloading of oxygen in the tissues is facilitated by lowering the oxygen affinity of haemoglobin (Hb) by both CO2 and diphosphoglycerate (DPG)1. This occurs because CO2 and DPG are oxygen-linked, that is, they are bound more firmly to deoxyhaemoglobin than to oxyhaemoglobin2,3. The binding of CO2 to Hb takes place by a reaction of CO2 with the α-amino groups to form carbamino compounds4,5, and binding curves can be measured by rather laborious methods4,6. Perrella et al.7 have modified these methods so that much smaller amounts of Hb, such as the specifically carbamylated Hbs8, can be used. In this method, Hb equilibrated with CO2 is rapidly taken to pH 11 to stabilise the carbamino CO2 and BioRad AG 1×8 resin added to remove carbonate and bicarbonate ions. The carbamino CO2 is displaced from the Hb by acidification and measured in a Van Slyke apparatus. DPG-free human deoxyhaemoglobin gave diphasic CO2 binding curves7 showing that the affinities of the α and β chain α-amino groups for CO2 are different, but it was impossible to establish which group had the higher affinity.

Therapy against brain swelling in stroke patients. A retrospective clinical study on 227 patients.

Abstract: The effectiveness of cerebral antiedema agents in stroke has been questioned. Animal and clinical work is inconclusive about steroids and osmotic drugs. A retrospective study of a continuous series of 227 stroke patients treated in the acute stage (some with dexamethasone alone, some with dexamethasone plus hyperosmotic mannitol infusions, and some without antiedema therapy) showed no significant difference in the ten-day survival rate. On this criterion, there is no ground for the systematic use of such agents against this type of brain swelling.