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Showing papers by "University of Milan published in 1976"


Journal ArticleDOI
TL;DR: Logistic curves have been fitted to the growth during puberty of the 55 boys and 35 girls of the Harpenden Growth Study who were measured every three months during puberty and thereafter until growth ceased.
Abstract: Logistic curves have been fitted to the growth during puberty of the 55 boys and 35 girls of the Harpenden Growth Study who were measured every three months during puberty and thereafter until grow...

442 citations


Journal ArticleDOI
TL;DR: Proteins with known isoelectric points (pI), as determined by isoeLECTric focusing, have been tabulated and, in the case of proteins displaying microheterogeneity, the major components have been indicated.

404 citations


Journal ArticleDOI
TL;DR: From an evolutionary view point, karyotype rearrangements of Robertsonian type may initiate reproductive isolation, which prepares the ground for further genetic diversification and, as in the case of the mouse, of incipient speciation.
Abstract: A survey is given on the occurrence, the geographic origin and the arm composition of 27 Robertsonian fusion metacentric chromosomes of wild populations of the mouse. Their study is of twofold interest: a) it is possible to introduce these naturally occurring metacentrics in laboratory strains for experimental use. At present, altogether 34 metacentric chromosomes of different composition are available including 7 cases of metacentrics known from laboratory strains of the mouse. b) With the search for metacentrics in the mouse and with their identification insights are permitted in the role of Robertsonian changes in the course of mammalian evolution — Several separate populations of the mouse with different sets of multiple (up to 9) metacentrics have been found in Switzerland and Italy. Some of the individual metacentrics may occur in different populations. The participation of an acrocentric autosome in the formation of metacentrics seem to be at random, but the sex chromosomes are never included in a metacentric. — Homology of the arms involved in metacentrics is conserved, so that in meiosis of interpopulation hybrids long chains or rings are observed. They may include up to 16 metacentrics arranged according to the alternating homologies of their arms. — Reduction of fertility of single or multiple metacentric heterozygotes and of the interpopulation hybrids is due to mechanisms of segregational imbalance and subsequent prenatal elimination of fetal offspring, but it follows also the pattern of male limited hybrid sterility. — From an evolutionary view point, karyotype rearrangements of Robertsonian type may initiate reproductive isolation, which prepares the ground for further genetic diversification and, as in the case of the mouse, of incipient speciation.

166 citations


Book ChapterDOI
TL;DR: Results strongly suggest that the treatment with gangliosides greatly influences the regeneration and reinnervation process of both cholinergic and adrenergic nerve fibers.
Abstract: There is now an increasing body of evidence to support the idea that Cns and Pns gangliosides may play an important functional role in various nervous tissues although their precise role has not yet been elucidated. There is also good biochemical evidence that gangliosides are highly concentrated in the nerve terminals, most of them associated with the nerve terminal plasma membrane (Burton, 1976; De Robertis et al. 1976; Morgan et al. 1976), nevertheless any clear relationship between the subcellular distribution of gangliosides within the different nerve terminal membranes and the normal chain of events involved in transmitter release and the overall synaptic economy has not been yet established. In spite of these uncertainties we thought that it might be useful to test the effects of gangliosides during the process of nerve regeneration and reinnervation of target tissues.

164 citations


Journal ArticleDOI
TL;DR: Evidence has been accumulating over the last few decades that benzene produces not only aplastic anemia, but also leukemia, and that the fatal cases of leukemia outnumber those of true aplasia, so case records of patients with acute or subacute leukemia have become SO numerous that they exceed those of fatal pancytopenia.
Abstract: Benzene has been known for almost a century as a powerful bone-marrow poison, leading to aplastic or hypoplastic anemia. It is now a rather widespread belief that any chemical capable of inducing severe bone-marrow damage must be assumed to be a potential leukemogen.’ Actually, evidence has been accumulating over the last few decades that benzene produces not only aplastic anemia, but also leukemia, and that the fatal cases of leukemia outnumber those of true aplastic anemia. In 1928 Delore and Borgomano described the first case of “benzene leukemia,” an acute leukemia in a worker so heavily exposed to benzene that none of his fellow workers could stand more than two months without becoming ill. Shortly after this first description, other cases of leukemia attributed to benzene were published. In 1932, Lignac gave 0.001 ml benzene in olive oil weekly to 54 white mice over a period of 17-21 weeks, and succeeded in producing six leukemias and two infiltrating aleukemic lymphoblastomas, whereas no cases of leukemia developed among 1465 mice taken as controls. Subsequent attempts to reproduce leukemia by injecting laboratory animals with benzene gave inconclusive results, because cases of leukemia also developed in the control animals almost to the same extent.4 Since then, reports of acute and chronic leukemia in man attributed to benzene poisoning have appeared in the literature in increasing number. In 1938 Penati and myself,5. in a critical survey of the available literature from the period 1928-1938, found, in addition to about 60 cases of fatal aplastic anemia, ten cases of benzene leukemia and also four other cases which fitted into neither the picture of aplastic anemia nor into that of leukemia, because of atypical findings, like, for instance, splenomegaly, reticulocytosis with erythroblastosis, leucocytosis with immature elements in the circulating blood, leukemoid reaction, and myeloid metaplasia in the spleen and liver. In 1945, in addition to a personal observation, Saital investigated another 23 cases of leukemia attributed to benzene, according to the literature, in which it was clear that there was a predominance of the acute forms over the chronic ones. Browning8 collected 61 cases from the literature up to 1960, acute cases outnumbering the chronic ones; 14 were cases of acute aleukemia, and 12 were erythroleukemia. Tareeff and coworkers 9 described 16 cases of leukemia (6 acute and 10 chronic) in workers in the USSR occupationally exposed to benzene for 4-27 years (average = 15 years). In three out of the six acute cases, a latent period of two to five years between the cessation of the exposure and the development of leukemia was noted. In the past two decades, case records of patients with acute or subacute leukemia, usually with leukopenia at some stage in the illness, have become SO numerous that they exceed those of fatal pancytopenia. This finding led us to suspect that many cases that had been considered as the acute terminal stage of an aplastic anemia or as a hemorrhagic aleukemia, prior to the introduction of bone-marrow puncture, may in fact have been examples of acute myeloblastic

134 citations


Journal ArticleDOI
TL;DR: The IRMA appears a useful tooi in the investigation of von Willebrand's disease and helps to identify two different types of the disease.
Abstract: Summary. A solid phase non-competitive immunoradiometric assay (IRMA) has been developed which allows measurement of factor VIII related antigen (VIIIR: AG) levels in normal plasma as low as 2.5 × 10−4 U/ml. The assay is based on the extraction of VIIIR: AG from test plasma by means of polystyrene tubes coated with a specific unlabelled anti-VIIIR: AG rabbit antiserum and subsequent labelling of the extracted antigen with 125I-labelled anti-VIIIR: AG rabbit IgG. The amount of radioactivity retained by the tubes (percentage bound) is proportional to VIIIR: AG concentration and a linear correlation is observed when logs of plasma dilutions (from 1 in 300 to 1 in 4000) are plotted against logits of percentage bound. The IRMA is technically simple, specific and reproducible. In 32 normal persons there was a highly significant correlation (r= 0.94) between IRMA and rocket electro-immunodiffusion assay (EIA) of VIIIR: AG plasma levels using the same antibody. IRMA has also been used to investigate 32 patients with von Willebrand's disease (vWd) in whom VIIIR: AG plasma levels were below the lowest measurable concentration using EIA (< 0.10 U/ml). In 17 patients with an autosomal recessive mode of inheritance and unusually severe symptoms, the markedly abnormal laboratory findings were consistent with the homozygous state. In 11 of these VIIIR: AG was < 2.5 × 10−4 U/ml and was extremely low in the remaining 6 (1.3 × 10−2 to 4 × 10−3 U/ml). In 15 patients the disease was familial (being transmitted as an autosomal dominant trait) and of moderate clinical severity; the IRMA or VIIIR: AG ranged between 1.2 × 10−1 and 4 × 10−2 U/ml. The assay thus appears a useful tooi in the investigation of vWd and helps to identify two different types of the disease.

131 citations


Journal ArticleDOI
TL;DR: It is thought that it would be of some interest to give a short account of the European and especially the Italian literature on benzene leukemias.

119 citations


Journal ArticleDOI
TL;DR: Renal hypertension of the two-kidney type is divided into three stages: in the first two phases removal of the abnormal kidney corrects the hypertension, and in the third phase because changes in the opposite kidney maintain hypertension.

115 citations


Journal ArticleDOI
TL;DR: Significant changes are observed in the lipid composition of very low density lipoproteins from normal and hypercholesteremic rabbits, particularly in the fatty acid composition of cholesterol esters, and in the relative distribution of phospholipids.

111 citations


Journal ArticleDOI
TL;DR: Fusion of these membranes does not result in a random intermixing of the molecular components of the participating membranes, which retain their structural identity; and the enlarged luminal plasmalemma reverts to its original size by a progressive, specific removal of the regions of low particle density from the cell surface.
Abstract: In the acinar cells of the rat parotid gland the two membranes participating in exocytosis, i.e., the luminal plasmalemma and the secretory granule membrane, are clearly distinguishable in freeze-fracture because of their different densities in particles. In order to obtain point-specific information about the fusion-fission of these two membranes that occurs during the secretory cycle, glands were studied at various times (5 min to 6 h) after stimulation with isoproterenol. We observed that, in the course of the release of secretion products and shortly afterwards, the enlarged luminal plasmalemma exhibits a mosaic organization consisting of an alternation of membrane patches of high (original plasmalemma) and low (fused granule membrane) particle density. The transition between these two patterns is usually sharp. Later, concomitant with the reformation of acinar canaliculi, the low particle density membrane is found at the cell surface but only bounding vacuolar infoldings, and then it finally disappears. These results suggest that (a) fusion of these membranes does not result in a random intermixing of the molecular components of the participating membranes, which retain their structural identity; and (b) the enlarged luminal plasmalemma reverts to its original size by a progressive, specific removal of the regions of low particle density from the cell surface.

104 citations


Journal ArticleDOI
Enrica Bosisio1, Corrado L. Galli1, G. Galli1, S. Nicosia1, C. Spagnuolo1, L. Tosi1 
TL;DR: Levels of free arachidonic acid and of prostaglandin F2alpha and E2 have been measured in both brain cortex and cerebellum of rats killed by focussed microwave irradiation, and after decapitation followed by ischemia.

Journal ArticleDOI
TL;DR: Bromocriptine injected to rats induces an increase of cAMP levels in the striatum in vivo, but does not stimulate striatal dopamine-sensitive adenylate cyclase but surprisingly antagonized the activation of this enzyme elicited by dopamine.

Journal ArticleDOI
TL;DR: In pancreatic lobules incubated in Ca2+-free Krebs-Ringer bicarbonate solution +0.5 mM EGTA tight junctions are first disarrayed and then break up into fasciae occludentes and small fibrillar fragments, which move laterally in the plane of the plasmalemma and often wind up around the gap junctions.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the morphology and distribution of intercellular junctions in normal oral epithelium of the rat and found that both tight junctions and lamellar bodies might be responsible for establishing the barrier, which would thus consist of multiple discrete sealing devices, able of establishing a number of successive slow down steps in the extracellular diffusion of solutes.

Journal ArticleDOI
TL;DR: Two new gangliosides were isolated in pure form from beef brain and were provisionally named Ganglioside G5a and G5b, both of which contain fucose and are a mixture of at least two isomeric disials containing N‐acetylneuraminic acid and N‐glycolylneura‐minic acid.
Abstract: — Two new gangliosides were isolated in pure form from beef brain. They were provisionally named ganglioside G5a and G5b. Ganglioside GSa is a monosialoganglioside containing fucose. Its basic neutral glycosphingolipid core is the gangliotetraose ceramide: Gal (1 —> 3) GalNac (1—> 4) Gal (1 —> 4) Glc (1—>) ceramide, most likely with β-linkages. Fucose is linked to the 2-position of external galactose, N-acetylneuraminic acid to the 3- position of internal galactose. Ganglioside G5b is a mixture of at least two isomeric disialogangliosides containing N-acetylneuraminic acid and N-glycolylneura-minic acid. The major isomer has the following structure: NeuNac (α,2—>3) Gal (β,1—>3) GalNac (β, 1 —> 4) (NeuNglα, 2 —> 3) gal (β,1—>4) Glc (β,1 —>)-ceramide. The minor isomer contains N-acetylneur-aminic acid and N-glycolylneuraminic acid in an inverted linkage position.

Journal ArticleDOI
TL;DR: Prothrombin-complex concentrates in combination with F.F.P.T. may therefore be used to allow liver biopsy to be performed safely in patients presenting with severe coagulation defects, and is found to be the least effective therapeutic regimen.

Journal ArticleDOI
TL;DR: Results showing the remarkable activity of FC in stimulating proton secretion in root segments are interpreted as indicating that FC activates in roots, as in a wide variety of other plant organs, an electrogenic mechanism of proton extrusion deeply involved in cation transport.

Journal ArticleDOI
TL;DR: Heart mitochondria isolated from rabbits subjected to intermittent treatment with adriamycin show a reduced respiratory control, resulting from increase in state 4b oxidation, while the ADP/O ratio measured in vitro is essentially unchanged.

Journal ArticleDOI
TL;DR: The hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release, and a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension.
Abstract: Present knowledge of the mechanisms regulating release of renin is reviewed with particular emphasis on neural factors. Evidence is given for a direct effect of renal innervation on beta adrenergic receptors in juxtaglomerular cells, and for the involvement of reflex release of renin in conditions such as tilting and acute salt depletion. Participation of neural and nonneural mechanisms of control is also shown to occur in other conditions, such as aortic constriction and hemorrhage. The view is held that neural sympathetic factors might explain some of the renin disturbances found in essential hypertension. First, in patients with high renin hypertension part of the hypertension is renin-dependent, and these pressor levels of renin seem to be neurally induced since they can commonly be suppressed by beta adrenoreceptor blocking agents. Second, the hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release. Therefore a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension and as a better guide to therapeutic management. Indeed, most of the available antihypertensive drugs act on sympathetic activity, body fluid volume or renin, and this multifaceted profile would provide more rational guidelines for treatment.

Journal ArticleDOI
TL;DR: The results are interpreted as indicating that FC stimulates in roots the same energy-dependent proton secretion mechanism previously shown to be activated by FC in stem, coleoptiles, leaves, cotyledons and embryos from dormant seeds.

Book ChapterDOI
01 Jan 1976
TL;DR: Both in the primary and secondary osteoarthritis three factors are present: A slanting inclination of the weight-bearing joint surface, the contraction of the adductor muscles due to pain and the progressive inclining toward the vertical of the resultant force R.
Abstract: Both in the primary and secondary osteoarthritis three factors are present: 1. A slanting inclination of the weight-bearing joint surface. In secondary osteoarthritis it may be congenital or have developed after birth. In primary osteoarthritis it is provoked by a progressive disintegration of cartilage and bone, due to many causes as yet unknown. 2. The contraction of the adductor muscles due to pain. 3. The progressive inclining toward the vertical of the resultant force R, caused by shifting the body’s center of gravity S5 toward the painful bearing hip in a monopodal support (Pauwels, 1961 – 1965b).

Journal Article
TL;DR: The liver-protective effects of silymarin have been investigated in isolated hepatocytes suspended in vitro in sucrose solutions of graded hypotonicity and chlorpromazine, a drug which belongs to the group of the so called "unspecific membrane stabilizers", was without effect in this test.
Abstract: The liver-protective effects of silymarin have been investigated in isolated hepatocytes suspended in vitro in sucrose solutions of graded hypotonicity. Cells preincubated with the drug at the concentration of 10(-4) M were found to be entirely resistant or relatively little affected when exposed to hypotonic solutions which have a lethal effect on a considerable proportion of the control liver cells, as shown by the determination in the cell preparations (1) of the proportion trypan blue-positive (broken) cells, (2) of the protein synthesizing capacity. The protection was reduced but not abolished upon removal of the drug and cell washing. A smaller effect was observed with a drug concentration of 10(-5) M. At 10(-6) M the effect was no longer detectable. Chlorpromazine, a drug which belongs to the group of the so called "unspecific membrane stabilizers", was without effect in this test.

Journal ArticleDOI
01 Oct 1976-Blood
TL;DR: A patient with clinical and laboratory evidence of disseminated intravascular coagulation associated with deep-vein thrombosis and pulmonary embolism developed a qualitative platelet abnormality characterized by a defective release reaction.

Journal ArticleDOI
TL;DR: The present data suggest that the primary failure in gonadotrophin secretion in anorexia nervosa occurs at hypothalamic level; moreover the data on TSH and PRL secretion also point to the existence of a hypothalamic disorder in this disease.
Abstract: The secretion of lutenizing hormone (LH), follicle-stimulating hormone (FSH), thyrotrophin (TSH) and prolactin (PRL, was studied in 17 women suffering from anorexia nervosa. The mean basal serum LH was reduced (8.4 +/- 0.8 SE mIU/ml; P less than 0.001 vs normal controls), while LH increase after gonadotrophin-releasing hormone (LH-RH) appeared to be normal in 9 cases and impaired in 6 cases. The mean basal FSH did not significantly differ from normal subjects (3.9 +/- 0.5 mIU/ml), while LH-RH administration elicited an exaggerated increase in 7 cases and a normal increase in 8 cases: the mean FSH response was significantly higher than in controls (P less than 0.02). Plasma oestradiol-17beta was reduced (20.4 +/- 0.4 pg/ml; P less than 0.001) while the serum testosterone levels were normal (0.73 +/- 0.09 ng/ml). Clomiphene administration induced an increase in gonadotrophins in only 1 out of 7 patients. The mean serum TSH concentration was normal (2.3 +/- 0.4 muU/ml), while serum thyroxine and triiodothyronine and free thyroxine index, thought generally in the normal range, were significantly lower than values obtained in a control group (6.1 +/- 0.4 mug/100 ml, P less than 0.005; 102.3 +/- 7.7 ng/100 ml, P less than 0.005; 3.8 +/- 0.3, P less than 0.05). Though the mean serum TSH increase after thyrotrophin-releasing hormone (TRH) was normal (12.0 +/- 2.3 muU/ml), there were 4 impaired and 1 exaggerated increases, and 8 patients showed a delayed and frequently prolonged response. The increase in serum T3 after TRH appeared lower than in normal subjects (36.3 +/- 1.8 ng/100 ml, P less than 0.001). Serum PRL levels in basal conditions were higher than in the controls (19.4 +/- 4.1 ng/ml, P less than 0.001) while the increase in PRL after TRH was exaggerated in only 2 patients. The present data suggest that the primary failure in gonadotrophin secretion in anorexia nervosa occurs at hypothalamic level; moreover the data on TSH and PRL secretion also point to the existence of a hypothalamic disorder in this disease.

Journal ArticleDOI
TL;DR: A simple and rapid method for the determination of brain γ-aminobutyric acid and the sensitivity of the method allows to measure GABA in micrograms of brain tissue.

Journal ArticleDOI
F. Cavagnini, U. Raggi1, P. Micossi1, A. Di Landro, Cecilia Invitti 
TL;DR: Results lend support to the concept of a physiological stimulating effect of serotonin on ACTH secretion and are compatible with the view that serotonin exerts its action chiefly at the hypothalamic level while LVP promotes ACTH release by a primary action on the pituitary.
Abstract: The effect of metergoline, a specific antiserotoninergic drug, on ACTH secretion was investigated in 29 normal volunteers and in 4 patients with increased ACTH production (3 with Addison's disease, 1 with Cushing's disease). In 15 normal subjects, a 4-day treatment with 10 mg daily of metergoline significantly blunted the ACTH response to insulin hypoglycemia. Mean peak ACTH values before and after treatment were, respectively, 333 +/- 39.2 (SE) and 235 +/- 38.8 pg/ml (P less than 0.05). The corresponding values of plasma cortisol were 29.6 +/- 2.96 and 20.5 +/- 2.67 mug/100 ml (P less than 0.05). In contrast, metergoline failed to affect the ACTH response to lysine-vasopressin (LVP) administered iv (8 subjects studied) and im (6 subjects studied). In 3 patients suffering from Addison's disease, an appreciable although not statistically significant lowering of the plasma ACTH levels was noted during metergoline administration. The mean pre- and post-treatment values of plasma ACTH in these patients were, respectively, 1116 +/- 192.2 and 666 +/- 100.8 pg/ml, 4240 +/- 50.0 and 3398 +/- 368.0 pg/ml, and 431 +/- 44.0 and 352 +/- 23.9 pg/ml. In one patient with Cushing's disease caused by a pituitary adenoma, metergoline did not appreciably modify plasma ACTH levels. Taken together, these results lend support to the concept of a physiological stimulating effect of serotonin on ACTH secretion. Moreover, they are compatible with the view that serotonin exerts its action chiefly at the hypothalamic level while LVP promotes ACTH release by a primary action on the pituitary.

Journal ArticleDOI
15 Jan 1976-Nature
TL;DR: In one southern Italian and one Pakistani patient with homozygous beta0 thalassaemia in which no detectable betaglobin synthesis occurs and no beta-globin messenger RNA is found, the gene for beta globin has been shown to be present using complementary DNA.
Abstract: In one southern Italian and one Pakistani patient with homozygous beta0 thalassaemia in which no detectable beta-globin synthesis occurs and no beta-globin messenger RNA is found, the gene for beta globin has been shown to be present using complementary DNA. This demonstrates that for these patients the imbalance in chain synthesis is not attributable to a gene deletion.

Journal ArticleDOI
TL;DR: Focussed microwave irradiation of the brain, a technique which instantaneously kills the animals, and which was used for the determination of brain basal levels of free fatty acids and free arachidonic acid, does not per se modify brain lipid and fatty acid composition.
Abstract: —The release of free fatty acids and especially of free arachidonic acid occurring in rat brain during ischaemia has been studied in essential fatty acid-deficient animals. Free fatty acid levels are lower in essential fatty acid-deficient brains before and especially after 5 min of ischaemia. The percentage of arachidonic acid, in respect of total free fatty acids, is similar in both control and essential fatty acid-deficient brains before ischaemia (0 min), but is greatly reduced in deficient brains in respect of controls after ischaemia (5 min). Total levels of free arachidonic acid are thus greatly reduced after ischaemia in the brain of essential fatty acid-deficient rats. Focussed microwave irradiation of the brain, a technique which instantaneously kills the animals, and which was used for the determination of brain basal levels of free fatty acids and free arachidonic acid, does not per se modify brain lipid and fatty acid composition.

Journal ArticleDOI
TL;DR: It is concluded that the loss of catalytic activity which parallels the dansylation of a lysyl residue occurs because this residue is essential for the binding of the pyridine nucleotide substrate.

Journal ArticleDOI
29 Jan 1976-Nature
TL;DR: In this article, the authors discuss X-ray emission from systems containing bright B stars with emission lines (‘Be’ stars) and the optical identification of the sources: it has been proposed that, A1118−61 and A0535+26, coincide with bright B star with emission line (Be)8,9, while A0621−00 is identified with a completely different object, which showed a nova-like behaviour optically, simultaneous with the X-rays outburst.
Abstract: SEVERAL transient X-ray sources with decay times of the order of weeks to months have been reported1; the discovery of four new sources of this type, A1118−61 (refs 2 and 3), A0535+26 (refs 4–6), A1742−28 (P. W. Sandford, personal communication), A1523−61 (ref. 7), in less than 1 yr of operation of the X-ray satellite Ariel V, indicates that these objects are rather common. Important for the understanding of this phenomenon is the optical identification of the sources: it has been proposed that, A1118−61 and A0535+26, coincide with bright B stars with emission lines (‘Be’ stars)8,9, while A0621−00 is identified with a completely different object, which showed a nova-like behaviour optically, simultaneous with the X-ray outburst10. Here we discuss X-ray emission from systems containing Be stars.