Showing papers by "University of Pavia published in 1978"

Bombesin-like immunoreactivity in the lung.

Abstract: THE first suggestion that the lung contained endocrine cells was made by Feyrter1 when introducing the concept of a diffuse endocrine or paracrine system, composed of epithelial ‘clear cells’. The presence of argyrophil cells in human and other mammalian lungs was later confirmed2,3 and it was shown that some of these cells contained amines, demonstrated by argent-affinity, formaldehyde-induced fluorescence (FIF), and the possession of neurosecretory type granules. They have variously been termed Feyrter cells4, Kultschitzky cells5, argy-rophil-fluorescent-granulated or AFG cells6, enteroch-romaffin-like cells7, neurosecretory cells8, pulmonary argyrophil cells9, endocrine or endocrine-like cells10,11, and possess APUD cell characteristics10–13. Endocrine cells are present within the bronchial and bronchiolar epithelium both as single elements and as groups of cells. Groups of innervated, endocrine-like cells termed neuroepithelial bodies have been demonstrated4. Some pulmonary endocrine cells contain 5-hydroxytryptamine10,14 and possibly other amines, but no peptide product has yet been identified in them. Said15 has proposed that the lung may produce a vasoactive peptide and it has subsequently been shown that the lung produces an angiotensin II-like peptide16,17 and two vasoactive peptides18, although the cellular origin of these peptides has not been established. Three major types of endocrine cell have been identified in human fetal lung (types 1, 2 and 3), a distinction based largely on the morphology of their secretory granules which are 110–200 nm in diameter12. Granules in the type-2 cell of the lung resemble those in P cells of the gut and pancreas19. The P-cell product has not been identified but it may be a bombesin-like peptide20. Bombesin is a tetra-decapeptide isolated from frog skin21 having a wide range of actions on the mammalian gastrointestinal tract and vasculature22. The similarity between P cells of the gut and certain granulated cells of the lung suggested that a bombesin-like peptide might be present in the human lung, and we report here the presence of bombesin-like immunoreactivity in human fetal and neonatal lung.

Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) im man

Abstract: Application of the semithin-thin section technique indicates that the previously proposed identification of the ultrastructurally-defined K cell with the immunocytochemically-defined GIP cell is essentially correct. The K cell is established as a distinct entity and the way is open for an explanation of its role in the physiology and pathology of the gastroenteropancreatic system.

Types of endocrine cells in the human colon and rectum.

Abstract: At least four types of endocrine-like cells have been detected histochemically in the mucosa of the human colon and rectum, i.e. argentaffin cells storing 5-hydroxytryptamine (5 HT) and non-argentaffin cells reacting with glucagon, somatostatin and bovine pancreatic peptide (BPP) antibodies. Ultrastructurally, four main types and three rare types of endocrine-like cells have been identified. Among the former cells were: (1) argentaffin EC1 cells, known to store 5 HT and substance P, (2) poorly argyrophil L cells, corresponding to the glucagon-immunoreactive cells storing enteroglucagon or glucagon-like immunoreactivity (GL1), (3) inconstantly argyrophil F-like cells, possibly corresponding to BPP-immunoreactive cells, and (4) fairly argyrophil H cells of unknown function. Rare D cells, corresponding to somatostatin cells, N cells, corresponding to neurotensin cells, and P cells, of unknown function, have been also found.

Disposition of sodium valproate in epileptic patients.

Abstract: 1 Serum levels of valproic acid have been determined at fixed intervals after the administration of single oral and intravenous doses (800 mg) to six epileptic patients receiving chronic treatment with other antiepileptic drugs. 2 Serum levels declined monoexponentially shortly after the intravenous administration. Biological half-lives averaged 9.0 +/- 1.4 h (s.d.). Volumes of distribution were 0.175 +/- 0.025 l/kg. There was a statistically significant negative correlation between volumes of distribution and serum half-lives (P less than 0.005). 3 After oral doses serum levels rose rapidly to peak values within 0.5--2 h. Biological availability was 96 +/- 9%. 4 Comparison with a previous study performed according to the same protocol in healthy volunteers showed significantly increased volumes of distribution and rates of elimination in the patients. Total serum clearance was 85% higher in the patients as compared to the healthy subjects (P less than 0.001). Possible explanations for these findings are discussed.

Pharmacokinetics of valproic acid after oral and intravenous administration

Abstract: 1 The kinetics of sodium valproate (di-n-propyl-acetate, Depakine®) have been studied in six healthy volunteers after administration of single oral and intravenous doses (800 mg). 2 Kinetic parameters were similar for both routes of administration. In all subjects absorption was rapid and complete. Half-lives ranged from 11-15 h. Apparent volumes of distribution were relatively low (0.147 ± 0.004 l/kg) and showed little variation amongst individuals. 3 The factors responsible for the poor correlation between dosage and serum levels during chronic treatment and therapeutic implications are discussed.

Multiple endocrine cell types in thyroid medullary carcinoma - Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells

Abstract: 10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types.

Ultrastructural similarity of endocrine-like cells of the human lung and some related cells of the gut.

Abstract: The ultrastructure of endocrine-like cells of the human lung was compared to the ultrastructure of endocrine-like cells of the stomach and pancreas in both adult and foetal material. Three types of endocrine-like cells were found in the human foetal lung. Type 1 or P1 cells contained very small granules (about 110 nm) of two varieties, cored and vesicular; type 2 or P2 cells with cored granules measuring about 130 nm; and type 3 cells with cored granules of about 180–190 nm. In the adult lung only one type Pa cells with cored granules could be found. Cells resembling foetal P1 cells were not found in foetal or adult gastric mucosa, or in the pancreas. In the gastric mucosa cells resembling pulmonary Pa or P2 cells were moderately represented and often difficult to distinguish from each other. Thus, they were grouped together as gastric P cells. Cells with granules resembling those of pulmonary type 3 cells were found most numerous in the adult oxyntic mucosa. Cells resembling gastric P cells (and pulmonary P2 cells) were rather numerous in foetal pancreas, but very rare in adult pancreas. Few cells containing granules somewhat resembling those of pulmonary type 3 cells were present in both foetal and adult pancreas. The results were discussed in respect to 1) the similarities between some gastric or pancreatic carcinoids and lung carcinoids, 2) the gastro-pancreatic P cells as a separate cell population, 3) the possible secretion by the lung endocrine-like cells of active substances, either amines or peptides, 4) the similarity between the secretory granules of Pa and P1 cells and neurosecretory granules of the hypothalamus and between P2 cells and some endocrine cells of the pituitary.

The ultrastructural localization of factor VIII-antigen in human platelets, megakaryocytes and endothelial cells utilizing a ferritin-labelled antibody.

Abstract: By means of electron microscopy combined with the use of monospecific anti-factor VIII-antigen (VIIIR:AG) antibodies conjugated to ferritin, the subcellular localization of VIIIR:AG in platelets, megakaryocytes and in endothelial cells has been established The reported results suggest the possibility that the megakaryocyte is able to synthesize VIIIR:AG and also to secrete it by means of a microcanalicular system similar to that present in the endothelial cell Platelets may derive their VIIIR:AG content partly from the megakaryocyte and partly from the plasma

Cerebral tumors induced by transplacental ENU: Study of the different tumoral stages, particularly of early proliferations

Abstract: Experimental cerebral tumors have been induced by transplacental ENU. A systematic diachronic study of the brains has been performed starting from the 15th day of extrauterine life. The tumoral lesions firstly appear as “early stage proliferations” or oligodendroglial foci and develop as glial micro-and macrotumors or as isomorphic and polymorphic oligodendrogliomas respectively.

Immunodeficiency in Down's syndrome: T-lymphocyte subset imbalance in trisomic children.

Abstract: In fourteen children with Down's syndrome the percentage of circulating T-cells forming rosettes with sheep erythrocytes, either in the presence or in the absence of foetal calf serum, was significantly lower than in appropriately matched controls. In contrast the percentage of T-cells forming rosettes with human erythrocytes was significantly higher in children with Down's syndrome than in controls. These data support the hypothesis that a defective T-cell maturation is an early integral feature of Down's syndrome.

Estimation of Ferrokinetic Parameters by a Mathematical Model in Patients with Primary Acquired Sideroblastic Anaemia

Abstract: Ferrokinetic parameters were estimated in eight patients with primary acquired sideroblastic anaemia (PASA) by means of a mathematical model of iron kinetics. Both plasma 59Fe clearance and red cell utilization curves were used to identify the model parameters. The close agreement between experimental and theoretical data proved that the model can describe iron kinetics in sideroblastic anaemia. Ineffective erythropoiesis was found to be the major factor in the production of the anaemia. Various degrees and patterns of peripheral haemolysis were observed. The storage iron was always markedly increased and a large non-erythroid iron turnover was calculated in the most severely affected patients. The results are compared with present knowledge of erythropoiesis in PASA.

Evidence for defective T cell function in patients with alopecia areata

Abstract: The role ofimmune factors in the pathogenesis of alopecia areata (AA) is still the object of considerable theoretical and experimental debate. Our interest in the problem was recently stimulated by the serendipitous finding ofa low percentage of circulating T lymphocytes in two subjects with AA. This finding prompted us to assess the percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes: T cells), as well as of lymphocytes forming rosettes with sheep erythrocytes coated with IgM antibody and complement (EAC rosettes: B cells) and of lymphocytes forming rosettes with human erythrocytes coated with anti-CD IgG antibodies (EA-rosettes: 'L' or 'null' cells) in 25 subjects affected by AA and in an equal number of ageand sex-matched healthy controls. In both groups the age ranged from 15 to 52 years and the male/female ratio was 7/18. All subjects were in good general health and were taking no drugs at the time of the study. The mean percentage of circulating T cells in subjects with AA {^yi6±2-<,6 s.d.) was much lower than that of controls (61-3±0-53 s.d.); Student's 'r'-test performed after angular transformation of the data showed that the difference between the two means was statistically significant (P< 0-005). ^^ the contrary, in the subjects with AA the mean percentages of B cells (12-4 + 0-6 s.d.) as well as of L cells (1814+1-8 s.d.) were not significantly different from those in controls (B cells: ii-2±o-8 s.d.; L cells: IO-24+O-9 s.d.). Ofthe 25 tested patients, only 7 had percentages of circulating T cells above 50 (the lower limit of normal range in our laboratory); 3 of the latter 7 patients were in remission, whereas all remaining patients had percentages of T lymphocytes below 50 and were in the active phase of the disease. Some groups have reported a high frequency of autoantibodies in AA (Cunliffe et aL, 1969; Main et al., 1975) and T lymphocytes are known to be involved in the control of autoantibody 'triggering' (Lachmann, 1975). Further studies are in course to clarify the clinical and pathogenetic significance of these findings and speculations.

Immunoglobulin G to virus-specific early antigens in congenital, primary, and reactivated human cytomegalovirus infections.

Abstract: Immunoglobulin G antibody to human cytomegalovirus (CMV)-specific early antigens (EA-Ab) was determined by the immunoperoxidase antibody technique in several cases of congenital, primary, and reactivated CMV infections. Mothers of congenitally infected infants and a group of leukemic children and pregnant women were also studied. In 11 cases of congenital infection, CMV EA-Ab was always associated with CMV excretion whether immunoglobulin M antibody was present or not. Nine mothers of congenitally infected infants had CMV EA-Ab for several months after delivery, but association with CMV elimination was not established when urine and/or saliva were tested for virus isolation. In all nine cases of primary CMV infection, CMV EA-Ab was present, and in five its detection was associated with CMV isolation. In one case, disappearance of EA-Ab occurred when virus excretion ceased. In five cases of reactivated CMV infections, a consistent association between CMV EA-Ab and virus isolation was found. Six of 31 leukemia children had CMV EA-Ab, and virus was isolated from 3 of these. Four of 28 pregnant women showed EA-Ab in their serum, but tests for isolation were not done. These data suggest that CMV EA-Ab is not a marker of a current primary CMV infection, as previously reported, but a marker of an active CMV replication which can take place in primary as well as in congenital and reactivated CMV infections. Images

Immunity in Down's syndrome.

Abstract: Dr. Ablin's letter and the reply by Seger and Str6der (Eur. J. Pediatr. 127, 149--152) have once again raised the debated problem of whether the immune derangements of Down's Syndrome (DS) are 'primary' (i.e., resulting from the genetic anomaly) or acquired as a result of institutionalization. Both in the letter and in the reply it is suggested that an answer to this problem is likely to result from a comparison of the immune status of institutionalized subjects with DS with that of institutionalized controls without DS. This need for a careful environmental matching has long been stressed. In this connection it might be of some interest to outline here some results of our immunologic studies of DS since they were obtained by comparing: (a) institutionalized subjects with DS with age and sex-matched chromosomally normal controls f rom the same i~tstitution and (b) non-institutionalized subjects with DS with chromosomally normal mental retarded matched for sex, age, and environmental conditions. Briefly: 1. Serum Ig levels were found to be age normal during the first five years of life; IgG and IgA increased thereafter to attain levels much higher then those of controls while IgM levels decreased slightly [5]. 2. Lymphocyte responsiveness to phytohemagglutinin (PHA) was comparable to that of controls during the first ten years of life, declining dramatically thereafter [5]. The percentage and absolute number of circulating T cells were significantly lower in DS than in controls from the first few months of life [3--5, 11]. 3. Autoantibodies directed against human thyroglobulin were present in about 40% of subjects with DS of age ranging from a few months to 50 years, while these autoantibodies were present in only about 20% of the matched controls [12]. In the same group ofprobands the rate of carriers of the Hepatitis B surface Antigen (HBs Ag) was more then 20% in subjects with DS and about 6% in controls [12]. Other groups, in studies appropriately planned with respect to environmental matching of DS probands with controls, have reported similar immune derangements in DS, i.e., dysgammaglobulinemia [2, 10], reduced lymphocyte responsiveness to PHA [1], low numbers of circulating T cells [7, 8] and high frequencies

Re-examination of the crystal structure of weberite

Abstract: The crystal structure of weberite, Na2MgAlF7, was redetermined from 3-dim. X-ray data and refined by least squares methods in space groupImma to a conventional reliability factorR=0.036. Mg and Al have octahedral 6-coordination. Two crystallographically independent kinds of Na atoms form different NaF8-polyhedra with the F atoms at the corners of a flattened hexagonal bipyramid and of a square prism, respectively.

Time Machine and Geodesic Motion in Kerr Metric

Abstract: The existence of nontrivial causality violation is a peculiar property of the space-time around a naked singularity. In the case of Kerr metric witha > m we have found that for a particular class of geodesies that could in principle violate causality, the conditions for causality violation are never satisfied.

Steady-state atomic fluorescence radiance expressions for continuum excitation

Abstract: Several general expressions for the atomic fluorescence radiance excited by a laser source are presented for both two-level and three-level systems. The laser has been approximated to a spectral continuum since its bandwidth is assumed to be much larger than the absorption profile. Two types of three-level systems are considered: (1) systems where two excited states are close together, both coupled radiatively with the ground state (Na, K, Cs, etc.); and (2) systems where one level is close to the ground state, both being radiatively connected with a third excited state (T1, In, Ga, etc.). Expressions are given for both linear and saturating conditions, and the use of such expressions for absolute species measurement is discussed. In our treatment, we have made the assumption that the rate equations approach is valid.

Polyclonal activation of human B lymphocytes in vitro by pokeweed mitogen: a simple technique for the simultaneous assessment of cell proliferation, generation of plasma cells, plaque-forming cells and immunoglobulin production.

Abstract: A simple technique has been worked out for the simultaneous assessment of cell proliferation, generation of plasma cells, plaque-forming cells and immunoglobulin production from single cultures of 1 X 10(6) human peripheral blood lymphocytes stimulated with pokeweed mitogen (PWM). Kinetic studies showed that number of cells, thymidine incorporation rate, number of plaque-forming cells against fluorescein-isothiocyanate-haptenated sheep erythrocytes and concentration of IgM and IgG in the supernatant peaked on the average between day 5 and 7 of culture. This technique is particularly suitable for the analysis of hypogammaglobulinaemias in infancy.

Behaviour of young and old desialylated rabbit erythrocytes in vivo.

Abstract: Young and old rabbit erythrocytes, separated by density gradient centrifugation, were desialylated by neuraminidase treatment and reinjected into the animal after 51Cr labelling. Both red cell populations are quickly removed from the circulation and trapped by the liver; then a large percentage of the young cells reappear in the peripheral blood and behaves like untreated erythrocytes; old cells, on the contrary, do not return to the blood stream and are probably lysed in the liver. These results suggest that a sialic acid repair can occur on the membrane of young erythrocytes and confirm that the loss of this molecule is not by itself sufficient to determine the death of the cell.