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Biomedical subjects

M Pietropaolo

Publications and source records attributed to M Pietropaolo.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pancreatic beta-cell destruction in non-obese diabetic mice.

We determined the natural history of the widespread pancreatic islet beta-cell destruction that precedes the onset of spontaneous putative autoimmune diabetes mellitus in NOD mice. For this purpose, we performed both histological and immunocytochemical examinations of pancreata retrieved from mice at 2 through 30 weeks of age. An overexpression of la antigens was identified on islet beta cells at 4 weeks of age, without evidence of mononuclear cell infiltration. The abnormal expression of la antigens was age-related and was associated with hyperexpression of class I antigens and progressive islet cell histologic damage after 17 weeks of age. Immunocytochemical examination of islet cell infiltrate showed that the number of macrophages did not increase during the early phase of islet cell damage in these mice. The L3T4/Lyt-2 ratio increased after 7 weeks of age, but was 1:1 in the late stage of insulitis. These findings suggest that widespread islet beta-cell destruction is a process that begins primarily with derangements of the pancreatic beta-cell immune pattern, which may trigger a mononuclear cell reaction.

Animals↗
PubMed1993

Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen.

We have identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM) by screening a human islet lambda gt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicts a 483-amino acid protein. ICA69 shows no nucleotide or amino acid sequence relation to any known sequence in GenBank, except for two short regions of similarity with BSA. The ICA69 cDNA probe hybridizes with a 2-kb mRNA in poly(A+) RNA from human pancreas, brain, heart, thyroid, and kidney, but not with skeletal muscle, placenta, spleen, or ovary. Expression of ICA69 was also detected in beta cells and cell lines, as well as in tumoral tissue of islet cell origin. The native ICA69 molecule migrates to 69 kD in SDS-PAGE as detected with specific antibodies. Serum samples from relatives of IDDM patients specifically reacted with affinity-purified recombinant ICA69 on Western blotting. The structural gene for ICA69 was designated ICA1. A homologue in the mouse, designated Ica-1 was mapped to the proximal end of chromosome 6 (within 6 cM of the Met protooncogene). ICA69 adds a novel autoantigen to the family of identified islet target molecules, and by the manner of its identification and characterization large amounts of antigen are available for development of quantitative, convenient predictive assays for autoantibodies and analysis of the role of this molecule in diabetes autoimmunity, as well as its physiologic function.

Amino Acid Sequence↗
PubMed1991

Immunoprotection of pancreatic islet grafts within artificial microcapsules.

To circumvent pancreatic islet graft-directed immune destruction we enveloped porcine islets within highly biocompatible and selectively permeable algin/polyaminoacid microcapsules. These special microspheres were deposited between the inner (permeable) and the outer (impermeable) layers of an artificial, coaxial vascular prosthesis, directly anastomized to blood vessels. Five dogs with spontaneous, insulin-dependent diabetes received microencapsulated porcine islets in arterio-vein iliac prosthesis by-passes. One showed complete and the remainder partial, sustained reversal of hyperglycemia. Microencapsulation may be a potential solution to immunological problems related to islet transplantation.

Animals↗
PubMed1990

A method for the massive separation of highly purified, adult porcine islets of Langerhans.

A method for the massive and reproducible isolation of highly purified, adult porcine islets of Langerhans is described. The successful combination of donor animal-strain selection with original procedures for pancreas retrieval and enzymatic digestion permitted us to separate uniquely massive concentrations of pure porcine islets with no need for mechanical disruption of the pancreatic tissue. Following our procedure, porcine islets, which fully retain viability and function, can be harvested easily and rapidly. Xenotransplantation of such islets, immunoprotected within algin/polyaminoacidic microcapsules, was associated with complete reversal of hyperglycemia in rodents with either spontaneous or streptozotocin-induced diabetes mellitus.

Animals↗
PubMed1990

[Islands of Langerhans transplant in the treatment of diabetes mellitus: current status, indications, future perspectives].

Islet cell transplantation is a potential and attractive alternative to exogenous insulin administration for the therapy of IDDM. Large scale clinical applicability of this approach has been hampered, so far, by technical problems such as separation of massive islet concentrations and immune rejection. Microencapsulation within algin/polyaminoacids has provided islets with selective permeable biomembranes thus allowing prevention of the host's immune response and circumvention of general immunosuppression of the recipient. This progress could offer new opportunities for islet cell transplantation in patients with IDDM.

Diabetes Mellitus, Type 1↗
PubMed1989

Insulin resistance in porphyria cutanea tarda.

It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

Adult↗
PubMed1986

Effects of beta non-selective and beta 1 selective adrenergic blocking agents on glucagon secretion from isolated perfused rat pancreas.

To characterize beta-receptors which affect pancreatic A-cell activity, the effects of propranolol (beta non-selective blockade) and metoprolol (beta 1 selective blockade) were evaluated on epinephrine modulated insulin (IRI) and glucagon (IRG) release both in basal state and during metabolic stimulus (arginine 20 mM). The isolated perfused rat pancreas model with the exclusion of stomach and duodenum was used. Epinephrine infusion (at 10(-7) M) caused a prompt and sustained increase in basal IRG secretion and significantly potentiated glucagon release in response to metabolic stimulus. Insulin secretion was markedly suppressed by epinephrine both in basal conditions and during metabolic stimulus. Propranolol (at 10(-7) M) and metoprolol (at 10(-7) M) infusion clearly and similarly counteracted epinephrine stimulatory effects on IRG secretion but failed to elicit any significant effect on the epinephrine inhibited IRI release either in basal state or during the metabolic stimulus. These results suggest that, at least in the rat, the adrenergic stimulation of IRG release is mediated through a beta 1 receptor.

Animals↗
PubMedDate not supplied

Platelet-leukocyte interactions in hemodialysis patients: culprit or bystander?

The formation of circulating platelet-leukocyte complexes has been observed in a variety of conditions and may be pathophysiologically significant. Platelet-leukocyte interactions in fact facilitate metabolic cooperation and mutual activation, which may be of relevance in many biological processes including inflammation, atherogenesis and hemostasis. During hemodialysis procedure, the series of reactions that can occur upon blood contact with the foreign membrane surface may involve a variety of changes affecting almost every cellular and plasmatic component of the blood. This article reviews the evidence for abnormal interactions between circulating platelets and leukocytes in uremic patients undergoing maintenance hemodialysis and the pathophysiologic implications which may stem from such interactions.

Animals↗
PubMedDate not supplied

Epidemiological aspects of cutaneous malignant melanoma (review).

There is an increasing interest in the etiology of cutaneous malignant melanoma (CMM). Once considered a rare tumour, CMM is now the fourth commonest cancer in Australia and New Zeland, the tenth in the Usa, Canada and Scandinavia and the eighteenth in Great Britain. The growing scientific concern on the urgent need to highlight the cause/s of CMM is well documented by the large number of well-designed and well-conducted epidemiological studies reported in the last two decades. Such studies facilitated testing of many etiological hypotheses derived from earlier descriptive investigations and contributed to significant progress in understanding the etiology of such disease. The quantification of the extent to which the increases in CMM incidence and mortality rates are related to new lifestyles and to new patterns of exposure to potential carcinogenetic agents is essential in order to establish an appropriate preventive strategy. In population of mainly European origin a substantial proportion of the increased incidence of CMM is attributable to steady change from predominantly occupational to predominantly recreational exposure to solar radiation. Therefore the present review puts particular emphasis on exposure to sunlight as well as to artificial ultraviolet light, as modifiable causes of CMM. Incidence and mortality data and other potential risk factors for the development of CMM will also be briefly reviewed.

Humans↗