Showing papers by "University of Milan published in 1982"

The 5alpha-reduction of testosterone in the neuroendocrine structures. Biochemical and physiological implications.

Abstract: Introduction It is now well established that the prostate and other androgen-sensitive peripheral structures (seminal vesicles, sebaceous gland, kidney, etc.) metabolize testosterone into 5α-androstane-17β-ol-3-one (dihydrotestosterone, DHT) and subsequently into 5α-androstane-3α, 17β diol (3α-diol) (1–6). In the peripheral androgen-responding tissues little amounts of 5α-androstane-3β,17β-diol (3β-diol) are also formed from DHT (7–9). These conversions occur under the influence of an enzymatic complex that includes a 5α-reductase, and two (3α- and 3β-) hydroxysteroid dehydrogenases. According to a theory which is now generally accepted, these 5α-reduced metabolites act as the intracellular mediators for many of the multiple actions testosterone exerts on its target structures (1–3, 10). A large group of in vivo and in vitro studies indicate that, in adult male mammals, the anterior pituitary (11–25) and several central nervous structures (in descending order: the hypothalamus, the midbrain, the amygdala,...

Paleogene magnetic stratigraphy in Umbrian pelagic carbonate rocks: The Contessa sections, Gubbio

Abstract: The Umbrian sequence of pelagic carbonate rocks provides an opportunity for precise correlation between Paleogene biostratigraphy and geomagnetic polarity history. The red-to-pink, Paleocene to middle Eocene Scaglia Rossa limestone, the varicolored upper Eocene Scaglia Variegata limestone, and the gray-green Oligocene Scaglia Cinerea marlstone form a 250-m-thick, continuous exposure in the Contessa Valley near Gubbio, Italy. Magnetostratigraphic, lithostratigraphic, and biostratigraphic investigations in three sections covering the entire Paleogene have confirmed and dated the geomagnetic reversal sequence for most of this period. The ferromagnetic mineral in the Scaglia Cinerea is magnetite and AF demagnetization to peak fields of 20 mT is sufficient to define the characteristic remanent magnetization. The Scaglia Variegata and pink Scaglia Rossa samples contain an additional hematite component which is very pronounced in dark red Paleocene Scaglia Rossa samples. Changes of magnetic mineralogy take place in these limestones during heating, especially above 500 °C. However, thermal demagnetization is effective in isolating the characteristic remanence vectors, which form almost antipodal clusters of directions representing normal and reversed polarities. The directions are rotated counterclockwise, partly due to post-Oligocene tectonism. Paleontological zonations of planktic foraminifera and calcareous nannofossils were hampered by poor preservation, but the major epoch and stage 29, as in the Gubbio Bottaccione section; Paleocene-Eocene, just above anomaly 25; Eocene-Oligocene, between anomalies 13 and 15; Oligocene-Miocene, just below anomaly 6C. These correlations require slight modifications to previous conclusions on Paleogene sea-floor spreading rates.

Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia.

Abstract: Hormonal studies and human leukocyte antigen (HLA) genotyping were performed in 5 males and 13 females who were demonstrated to have 21-hydroxylase deficiency. The enzymatic deficiency of steroidogenesis was detected by family studies of 10 females who presented with varying symptoms of androgen excess. The 10 index cases had normal genitalia at birth, but virilized to varying degrees postnatally. The additional 8 affected family members had not sought medical care, but some were found to have signs of virilization on physical examination, while others were normal. Thus both late-onset (symptomatic) and cryptic (asymptomatic) 21-hydroxylase deficiency occurred in the same pedigree. The hormonal and genetic linkage studies indicate that the late-onset (symptomatic) form of 21- hydroxylase deficiency, like the cryptic (asymptomatic) and classical forms of 21-hydroxylase deficiency, is transmitted by an autosomal recessive gene which is linked to HLA-B. Furthermore, the classical form of 21-hydroxylase defic...

Comparison of Cardiovascular, Renal, and Humoral Effects of Acute Administration of Two Calcium Channel Blockers in Normotensive and Hypertensive Subjects

Abstract: The acute effects of two calcium channel blockers, nifedipine and verapamil, were compared in eight normotensive subjects and eight patients with essential hypertension. Nifedipine 10 mg and verapamil 160 mg orally had no effect on blood pressure of normal subjects, but reduced systolic and diastolic pressures of hypertensive patients to the same extent. The blood pressure reduction caused by nifedipine was more prompt and of lesser duration than that caused by verapamil. In both normal subjects and hypertensive patients nifedipine caused a transient rise in heart rate and plasma renin activity, and plasma catecholamines showed a tendency to increase; verapamil did not affect these variables. Nifedipine induced a marked increase in urine volume and renal sodium excretion in hypertensive patients, with a much smaller change in normotensives. Verapamil did not influence water and sodium excretion in either direction. Thus, this study shows similarities and differences between the effects induced by acute oral administration of the most-used vasodilating calcium antagonists.

The role of the autonomic nervous system in sudden coronary death.

Abstract: The question of the role of the autonomic nervous system in sudden death is of paramount importance because, if fully elucidated, it may give critical insights into the basic mechanisms that lead to ventricular fibrillation and may provide the rationale for prevention. This article does not intend to review the entire question of the relationship between the autonomic nervous system and sudden coronary death since this subject or part of it has been largely dealt with in recent reviews;1-5 rather, it aims at providing updated information 011 recent progress in this area with particular reference to the role of cardiac sympathetic nerves and to the development of appropriate animal models specifically designed for the study of neurally mediated life-threatening arrhythmias. The cardiovascular effects of autonomic nerves are often studied by using the technique of electrical stimulation, which, although valuable in identifying neural circuits, is limited because it shows the artificial effect of massive activation of all nerve fibers present in the stimulated nerves, a very unlikely event in a system characterized by an extreme degree of specificity.6 We believe that the importance of the autonomic nervous system in relationship to pathophysiologic events which occur in real life situations, such as sudden coronary death, can be best studied by the use of selective denervation. In this way the resultant effects are due to the absence of the tonic sympathetic or vagal activity physiologically present in the nerves under investigation and it is possible to meaningfully compare what happens when the nerves are present and when they are absent. An attempt to understand the role of the autonomic nervous system in sudden coronary death requires a knowledge of the neural events associated with acute myocardial ischemia, of the effects of neural activity on coronary blood flow, and of the autonomic effects on cardiac electrical stability in ischemic and nonischemic hearts. It requires also the potential of developing relevant animal models in which adequate manipulations of the autonomic

Pancreatic effects of ethionine: blockade of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis

Abstract: Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet for 24 h develop hemorrhagic pancreatic necrosis with a 5-day mortality rate of approximately 50%. At the end of the diet administration, the in vivo discharge of digestive enzymes is blocked, images of exocytosis and luminal membrane recycling disappear, and zymogen granules accumulate within acinar cells. The general ultrastructure, however, remains well preserved, protein synthesis is normal, and intracellular transport of secretory proteins is only slightly retarded. Thus, the CDE diet does not affect the general phenomenon of membrane fusion-fission but specifically inhibits that associated with exocytosis. Twenty-four hours after withdrawal of the CDE diet, discharge of zymogen granules into lysosomes (crinophagy) can be observed, and, 24 h latr, autophagocytosis is noted. Finally, shortly before the onset of pancreatic necrosis, cells of nearly normal appearance are noted to be scattered among cells showing varying degrees of lesion up to complete disruption. Thus, the CDE-induced pancreatic necrosis results from a sequence of events: blockade of exocytosis evolves to crinophagy and autophagy, which might lead to lysosomal activation of zymogens.

The QT interval throughout the first 6 months of life: a prospective study.

Abstract: A prospective electrocardiographic study was designed to establish baseline values for electrocardiographic measurements, with specific reference to the QT interval during infancy, and to test the "QT hypothesis" for the sudden infant death syndrome (SIDS). In this ongoing study, ECGs are recorded on the fourth day of life and in the second, fourth and sixth months. The state of health at 1 year is ascertained by a phone call. So far, 4205 newborns have been enrolled. The mean QTc (QT interval corrected for heart rate) was 397 +/- 18 msec (+/- SD) at the fourth day, 409 +/- 15 msec (p less than 0.0001) at the second month, and 406 +/- 15 msec at the fourth month; by the sixth month, it returned to 400 +/- 14 msec. In 88 newborns, the QTc increased by over 40 msec at the second month. Among the 2000 infants checked at 1 year, there have been three sudden and unexpected deaths. The QTc of one of the victims at the fourth day was 563 msec, which exceeded the mean by more than 9 standard deviations, while the QTc of the other SIDS victims exceeded the mean by more than 2 and 3 standard deviations. These results are consistent with the "QT hypothesis," but more data are necessary before any conclusion on the potential relationship between QT interval prolongation and SIDS can be drawn. This study provides definitive waking normal values for QT interval in infancy and indicates that the QT interval lengthens physiologically and temporarily during the first months of life. In some infants, this lengthening may transiently impair cardiac electrical stability.

No classical type IIB fibres in dog skeletal muscle.

Abstract: To analyse the fibre type composition of adult dog skeletal muscle, enzyme histochemistry, immunohistochemistry for type I, IIA and IIB myosins, and peptide mapping of myosin heavy chains isolated from typed single fibres were combined. Subdivision of type II fibres into two main classes according to the activity of the m-ATPase after acidic and alkaline preincubation proved to be rather difficult and was only consistently achieved after a very careful adjustment of the systems used. One of these sub-classes of type II fibres stained more strongly for m-ATPase activity after acidic and alkaline preincubation, was oxidative-glycolytic and showed a strong reaction with an anti-type IIA myosin. The other one, however, although unreactive with anti-IIA myosin, was also oxidative-glycolytic, and only showed a faint reaction with an anti-type IIB myosin. Peptide mapping of the myosin heavy chains of typed single fibres revealed two populations of heavy chains among the type II fibre group. Thus, in dog muscle, we are confronted with the presence of two main classes of type II fibres, both oxidative-glycolytic, but differing in the structure of their myosin heavy chains. In contrast to some reports in the literature, no classical type IIB fibres could be detected.

Polyamines in mammalian tumors. Part I.

Abstract: Publisher Summary This chapter investigates the links between polyamines and tumors. It is particularly interesting to modify the culture conditions to clarify the influence of the environmental milieu on the activities of the polyamine biosynthetic enzymes by enhancing or decreasing the levels of these enzymes to see the role of polyamines in the cell growth process. To this purpose, several studies have been carried out with rat hepatoma cells growing in culture. Studies of the effects of growth conditions on ornithine decarboxylase (ODC) activity presents evidence that dilution of high-density hepatoma cell cultures with fresh medium results in a very large and transient increase in enzyme activity. Furthermore, among the factors affecting the growth conditions of the cultured cells, the addition of fresh medium or serum to the culture has been demonstrated to be one of the most important for a variety of other cell lines. In spite of the decades of research, most of the role of polyamines in eliciting the peculiar neoplastic behavior and in permitting invasive neoplastic growth remains unclear.

<33,000-yr K–Ar dating of the volcano–tectonic horst of the Isle of Ischia, Gulf of Naples

Abstract: The Gulf of Naples corresponds to a tectonic sink connected with recent volcanic activity in the South-Campanian area (Phlegrean Fields, Ischia and Vesuvius) At its extreme northwest, the Isle of Ischia was early recognized as a volcano-tectonic horst by Rittmann1 Previous data2 concluded that its uplift ended around 300,000 yr, and that the Green Tuff formation, of which it is predominantly composed, had an age of some 700,000 yr But tectonic and morphological studies, together with original tephrostratigraphical observations on the slope of the horst, led us to do some new K–Ar datings These revealed that the 780 m uplift of the horst from the sea level is younger than 33,000 yr; the Green Tuff, which was considered to be the oldest volcanic unit in the island is now dated at 56,000 yr, its eruption following the dismantlement of a first volcanic complex now dated as not older than 130,000 yr

Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects.

Abstract: Regular or crystalline insulin with sodium glycocholate as surfactant administered intranasally to normal volunteers induced hypoglycaemia and an increase in serum immunoreactive insulin concentrations. Serum C-peptide concentrations decreased or remained unchanged. Insulin administered intravenously to three of these subjects yielded a potency ratio of 1:8 for intranasal and intravenous insulin. In four insulin-dependent diabetics a cross-over study was performed on different days, insulin being administered once intranasally and once subcutaneously in a ratio of 1:9. In these patients the intranasal insulin was more effective than the subcutaneous insulin in preventing hyperglycaemia after breakfast. In four other insulin-dependent diabetics 11-hours monitoring was performed twice on two different days, insulin being administered in divided dosage sufficient to achieve a reasonable glycaemic profile. The administration during the morning, whereas subcutaneous insulin was more effective than intranasal during the afternoon.

Decreased CSF Concentrations of Homovanillic Acid and γ-Aminobutyric Acid in Alzheimer's Disease: Age- or Disease-Related Modifications?

Abstract: • Fifteen patients, 48 to 72 years old, with Alzheimer's disease were studied. Clinical status was assessed by neurologic and neuropsychologic examinations and psychometric testing. Patients were divided into two groups on the basis of clinical assessment: group 1, little mental deterioration, and group 2, serious mental deterioration. Nineteen subjects, 27 to 72 years old, without neurologic disease served as controls. Levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and γ-aminobutyric acid (GABA) were determined in lumbar CSF by fluorimetric or radioreceptor binding (GABA) methods. The HVA concentrations increased with age in the controls, whereas the GABA levels decreased with age, and 5-HIAA levels were not modified. When compared with the age-matched controls, the patients with Alzheimer's disease showed low concentrations of HVA but not of 5-HIAA or GABA. The decrease in HVA level was more pronounced in patients with severe mental deterioration and therefore appeared to be disease related.

The deletion in a type of delta 0-beta 0-thalassaemia begins in an inverted AluI repeat.

Abstract: In hereditary persistence of fetal haemoglobin (HPFH) and delta 0-beta 0-thalassaemia, increased levels of fetal haemoglobin (HbF) are found in adult individuals. HbF production is particularly noticeable in the former condition in which HbF levels of 20-40% are found in heterozygous patients, as opposed to 5-20% in delta 0-beta 0-thalassaemia. In a minority of these cases, no obvious abnormalities have been found in the globin gene region by DNA mapping, indicating that small deletions or perhaps even point mutations in critical DNA sequences in the globin gene cluster may be responsible for these conditions. However, most cases of HPFH and delta 0-beta 0-thalassaemia are associated with extensive deletions in the globin gene cluster. Genetic data and gene mapping investigations provided some evidence for the location of a regulatory area, whose deletion results in continuing activity of gamma-globin genes in adults, in a DNA region between the A gamma- and delta-globin genes, possibly 3-4 kilobases (kb) 5' to the delta gene. The precise nature of these sequences is of great interest, because it might help elucidate the molecular mechanisms regulating globin gene expression during development. Recently, Jagadeeswaran et al. cloned the DNA encompassing the region of a gene deletion in a type of HPFH and showed that the 5' end point of the deletion lies in the middle of an AluI repetitive DNA sequence. We have now cloned the corresponding region from the DNA of a delta 0 -beta 0-thalassaemia patient and we report here that the deletion ends in a different AluI sequence, congruent to 700 nucleotides 3' to the AluI repeat involved in the HPFH deletion, and in the opposite orientation.

Modification of the antinociceptive effect of morphine by centrally administered diazepam and midazolam

Abstract: 1 Intracerebroventricular administration of diazepam or midazolam decreased the antinociceptive effect of morphine in rats as measured by the "tail flick" method 2 Midazolam, injected into the periaqueductal grey matter (PAG) antagonized the analgesic effect of morphine The action of midazolam was partially reversed by bicuculline 3 These findings support the view that the effect of benzodiazephines on morphine antinociception may be mediated through gamma-aminobutyric acid receptors

Modification of arterial baroreflexes by captopril in essential hypertension.

Abstract: Captopril lowers blood pressure without increasing heart rate and plasma norepinephrine, which suggests that this drug may potentiate arterial baroreflexes. In eight subjects with untreated essential hypertension, blood pressure was monitored intraarterially and the effects of baroreceptor stimulation or deactivation were assessed by measuring (1) the slopes of the relations between increase or reduction in systolic pressure (intravenous phenylephrine or nitroglycerin) and the resulting lengthening or shortening in R-R interval, and (2) the increase or decrease in mean arterial pressure induced by increasing and decreasing carotid transmural pressure (neck chamber). The measurements were made before and after a hypotensive oral dose of captopril (50 mg). Before captopril, the slopes of the R-R interval changes with increase and reduction in systolic pressure were 8 and 4 ms/mm Hg, respectively. The slopes of the mean arterial pressure changes with increase and reduction in carotid transmural pressure were 0.51 and 0.40 mm Hg, respectively. After captopril, the responses to baroreceptor stimulation were unaltered but those to baroreceptor deactivation were augmented. The presser and heart rate responses to hand-grip and cold exposure were unchanged by captopril. Administration of captopril is accompanied by a baroreflex potentiation which involves the lower portion of the stimulus-response curve of the reflex. This phenomenon (which may originate at the afferent baroreceptor fibers or centrally) may avoid a reduction in the tonic baroreflex influence during captopril-induced hypotension, thus contributing to the hemodynamic effects of the drug.

Male gametophytic selection in maize.

Abstract: There is evidence that male gametophyte selection is a widespread phenomenon in higher plants. The pollen tube growth rate is one of the main components of gametophyte selective value; genetic variability for this trait, due to the effect of single genes or to quantitative variation, has been described in maize. However, indication of gametophytic selection has been indirectly obtained; its effect was revealed by the positive relation observed between gametophyte competitive ability and sporophyte metrical traits. This paper considers the results of selection applied to gametophyte populations produced from single plants. The competitive ability of the lines was evaluated in comparison with that of a standard line by means of the pollen mixture technique. Sporophytic traits were measured in the hybrid progeny obtained by crossing selected S3 and S4 families with an unrelated single cross and an inbred line. Gametophyte selection produced inbred lines with high gametophyte competitive ability. In view of the selection procedure adopted, this result was interpreted as an indication of haploid expression of genes involved in the control of pollen tube growth. Moreover, this gametophytic trait was positively correlated with sporophytic traits (seedling weight, kernel weight and root tip growth in vitro), indicating that both groups of characters have a common genetic basis.

Studies on α‐Latrotoxin Receptors in Rat Brain Synaptosomes: Correlation Between Toxin Binding and Stimulation of Transmitter Release

Abstract: alpha-Latrotoxin (alpha-LT), the major component of black widow spider venom, is a high-molecular-weight protein that acts presynaptically by stimulating the release of stored neurotransmitters. The purified toxin was iodinated to high specific radioactivity by the Bolton-Hunter procedure, without appreciable loss of biological activity. By the use of the 125I-toxin, specific receptors were revealed in synaptosome fractions isolated from various regions of the rat brain, but not in nonneural tissues. The density of alpha-LT receptors [which are probably composed of, or include, membrane protein(s)] varies between 0.6 and 0.88 pmol/mg of synaptosome protein, their affinity is very high (KA of the order of 10(10) M-1), their association rate is fast, and their dissociation rate slow. They might belong to a single, homogeneous class. This last conclusion, however, is still uncertain, because results suggesting a possible heterogeneity were obtained by studying the dissociation of the toxin from synaptosomes incubated in high-salt buffer. Experiments in which the binding of alpha-LT and its dopamine release activity in striatal synaptosomes were investigated in parallel in a variety of experimental conditions support the hypothesis that occupation of the high-affinity receptors is the initial step in the alpha-LT activation of the presynaptic response.

Excessive daytime sleepiness: a 1-year study in an unselected inpatient population.

Abstract: A prospective epidemiological investigation of excessive daytime sleepiness (EDS) was carried out in an unselected inpatient population admitted to a general hospital during a 1-year period. The study comprised 2518 patients, 1347 female and 1171 male, aged 6-92 years (mean, 55.2). On the basis of histories and clinical and polysomnographic data, EDS was found in 28 cases (1.11%). Of these, 25 (0.99%; 18 female and 7 male; mean age, 61.3) had sleep apnea syndromes (SAS) with predominantly obstructive apnea. Two patients (0.07%; one female and one male; mean age, 65.5) had idiopathic CNS hypersomnia, and one male patient (0.03%) aged 48 years had a combination of narcolepsy and SAS. Differences and agreements of our findings with previous literature data are discussed. The present study shows that in an unselected inpatient population, EDS is a relatively common sleep disorder, usually found in mild to moderate forms. Because it is not severe, it disturbs only relatively domestic activities of elderly retired patients or others who do not work outside the home, and is often masked by other troubles. For these reasons, EDS in the aging population may pass unnoticed in epidemiological studies based only on data from sleep disorder centers.