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Biomedical subjects

A Signore

Publications and source records attributed to A Signore.

At least 55 records · Page 3Linked to original sources
PubMed1995

111In-octreotide scintigraphy in metastatic medullary thyroid carcinoma before and after octreotide therapy: in vivo evidence of the possible down-regulation of somatostatin receptors.

We have investigated the presence of somatostatin receptors on the cell surface of metastatic medullary thyroid carcinoma in vivo using 111In-Octreotide scintigraphy. Five patients were studied before and three months after therapy with octreotide (300-600 micrograms/day). After each 111In-Octreotide scintigraphy the target/background (T/B) radioactivity ratio was calculated for each detectable metastases. A total of 14/18 metastases showed a reduction in the T/B ratio after therapy, suggesting saturation or down-regulation of the somatostatin receptors on metastases induced by octreotide therapy. Patients also showed a reduction in serum calcitonin levels after therapy. We conclude that 111In-Octreotide scintigraphy may be useful in medullary thyroid carcinoma to evaluate the rationale for somatostatin therapy and to monitor the effect of treatment.

Adult↗
PubMed1994

Histological study of pancreatic beta-cell loss in relation to the insulitis process in the non-obese diabetic mouse.

Non-obese diabetic (NOD) mice spontaneously develop an autoimmune diabetes with higher incidence in females than in males. In order to elucidate possible factors involved in the different incidence of diabetes between male and female mice, we studied the progression of pancreatic beta-cell loss in relation to mononuclear cell infiltration of the pancreas (insulitis). We examined the pancreas of 76 NOD mice (39 males and 37 females) of different ages. The beta-cell content was assessed by immunoperoxidase staining of sections with an anti-insulin serum and the severity of insulitis was determined by haematoxylin staining of the same sections. A semi-quantitative criterion was used to grade both parameters. The results showed that females have a faster loss of beta-cell mass, which progressively decreases with the increase of severity of insulitis. In males, a medium to severe degree of insulitis is required before initial loss of beta cells occurs. Under the age of 10 weeks there was a significantly lower content of beta cells in females than males (2.84 +/- 0.03 vs 2.67 +/- 0.07; P = 0.02). Since we never observed a significant difference in the degree of mononuclear cell infiltration in age-matched males and females, these data support the hypothesis of weaker beta-cell resistance to immunological attack in female mice. Thus beta-cell sensitivity, in addition to immunological activity, is an important factor in the pathogenesis of insulin dependent diabetes.

Aging↗
PubMed1994

New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2.

Insulitis is considered the histopathological hallmark of type I (insulin-dependent) diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, we have labelled recombinant interleukin 2 with 123I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. We studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled alpha-lactalbumin was used as the control protein. In the first set of experiments we studied the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled alpha-lactalbumin (p < 0.003 at 20 min: p < 0.001 at 40 min; p < 0.001 at 60 min) or Balb/c mice injected with labelled interleukin 2 (p < 0.05 at 40 min; p < 0.001 at 60 min). In another set of experiments, gamma camera images have been acquired after injection of 123I-labelled interleukin 2. Radioactivity in the pancreatic region of prediabetic NOD and Balb/c mice showed similar kinetics to those observed by single organ counting, with higher accumulation in the pancreatic region of NOD mice (p < 0.04 after 22-45 min in NOD mice vs Balb/c mice).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Combination of nicotinamide and steroid versus nicotinamide in recent-onset IDDM. The IMDIAB II Study.

OBJECTIVE: The aim of this study was to compare the effect of nicotinamide (NCT) alone or in combination with a cortisone-like substance, deflazacort (DFL), on the integrated parameters of metabolic control in patients with the recent-onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Thirty-six patients who were diagnosed with diabetes between 5 and 35 years of age entered a randomized, double-blind, 1-year prospective study. Group A (n = 18) received NCT for 1 year (25 mg.kg-1.day-1) plus DFL for 3 months (0.6 mg.kg-1.day-1 in the first month, 0.3 mg.kg-1.day-1 in the other 2 months). Group B (n = 18) received NCT for 1 year (25 mg.kg-1.day-1) plus placebo for the first 3 months. All patients were treated with intensified insulin therapy. RESULTS: At 3 months after diagnosis, the insulin dose was significantly higher in group A compared with group B (P < 0.03) with similar HbA1 levels. Basal and stimulated C-peptide levels in group A of both adults and children were significantly higher compared with patients of group B (P < 0.05 and P < 0.03, respectively). At the end of a 1-year follow-up, basal C-peptide did not differ between the two groups, although stimulated C-peptide was still significantly higher in patients of group A compared with group B (P < 0.05). Finally, insulin requirement did not differ between the two groups. CONCLUSIONS: A short-term course of DFL therapy at diagnosis in addition to NCT slightly increases glucagon-stimulated but not basal beta-cell function after 1 year.

Adolescent↗
PubMed1993

A simple method for the evaluation of receptor binding capacity of modified cytokines.

We have developed a flow cytometric method to evaluate the binding of interleukin-2 analogues to receptors. The method relies on competition for binding between a fluorescein-conjugated monoclonal antibody (MoAb) directed against the human interleukin-2 receptor alpha chain (fluorescein isothiocyanate (FITC) anti-IL-2R) and the test protein. IL-2R positive cells are incubated with FITC-anti-IL-2R MoAb in the presence of native IL-2 or IL-2 iodinated by either the chloramine-T or the lactoperoxidase-glucose-oxidase method. The binding of IL-2 is indicated by decreased fluorescence. This method is suitable for measuring the binding capacity of modified IL-2 molecules and avoids the need for radioactive tracers. It provides a simple and reproducible technique, which can be extended readily to the study of the receptor binding capacity of cytokines conjugated with toxins, drugs or other molecules.

Antibodies, Monoclonal↗
PubMed1993

Tolbutamide reduces the incidence of diabetes mellitus, but not insulitis, in the non-obese-diabetic mouse.

The functional state of beta cells may influence the rate of their destruction in Type 1 (insulin-dependent) diabetes mellitus. We examined the effect of diazoxide, which inhibits insulin secretion, or tolbutamide, which stimulates insulin secretion, upon the incidence of diabetes in the non-obese-diabetic (NOD) mouse. Female mice were treated from 3-30 weeks of age with diet containing diazoxide 250 mg.kg-1 or tolbutamide 125 mg.kg-1. The cumulative incidence of diabetes at 35 weeks was similar in the diazoxide (16 of 24) and control (18 of 24) groups, but reduced in the tolbutamide group (10 of 23, p < 0.04 vs control group). In a second experiment, treatment was started from 9 weeks of age, by which time insulitis is already present. The cumulative incidence of diabetes at 35 weeks was 16 of 24 in controls, 15 of 24 on diazoxide and 11 of 24 on tolbutamide (p = NS vs control). A third experiment compared the effect of treatment from 3 weeks with control diet or diet containing tolbutamide 125 mg.kg-1 or 500 mg.kg-1. Diabetes was reduced by tolbutamide treatment, with a cumulative incidence of 25 of 31 in controls, 18 of 30 on tolbutamide 125 mg.kg-1 (p < 0.04) and 14 of 32 on 500 mg.kg-1 (p < 0.002), although the difference between the two treatment groups failed to reach statistical significance. A fourth experiment showed that treatment from 3-12 weeks with diazoxide 1000 mg.kg-1 increased the extent of insulitis compared with controls and animals treated with tolbutamide 500 mg.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

NOD mouse colonies around the world--recent facts and figures.

Non-obese diabetic (NOD) mice are commonly used in autoimmune research. However, the diversity of these mice in developing autoimmune disease under different conditions prompted a group of researchers to compile a questionnaire on this subject. Here Paolo Pozzilli and colleagues comment on the results of this survey.

Age Factors↗
PubMed1993

The effect of a heparin analogue, ITF-5005, on diabetes incidence and insulitis in the non-obese diabetic mouse.

It has been suggested that heparin and its analogues may have a suppressive effect on the immune response by interfering with T-lymphocyte heparinase activity, thus altering the ability of T-lymphocytes to penetrate the extracellular matrix and migrate to target tissues. We have investigated whether a heparin analogue (ITF-5005) can alter lymphocytic infiltration of the endocrine pancreas (insulitis) and/or diabetes incidence in the non-obese diabetic (NOD) mouse. Sixty-four NOD mice were divided at weaning and injected subcutaneously five times per week with either 18, 36 or 72 micrograms/kg body weight of ITF-5005 or saline as a control. At 12 weeks of age, the animals were culled and their pancreata sectioned, stained and assessed 'blind' for insulitis and insulin containing cells. Insulitis was similar in all groups as was the proportion of insulin-containing cells. To determine the effect on diabetes incidence, two groups of mice were injected with either saline or 140 micrograms/kg body weight of ITF-5005 from weaning until 30 weeks of age. No difference was found in overall diabetes incidence; however, disease onset was significantly accelerated in the treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of insulin-containing cells found in the pancreas, but that it can accelerate the course of diabetes in the NOD mouse.

Animals↗
PubMed1992

Immunotherapy with ciamexon in the non obese diabetic (NOD) mouse.

Ciamexon (CMX), a new immunomodulatory compound acting mainly on B-lymphocytes was given orally to 42 NOD mice divided into three sex and litter matched groups (A: 0.3 mg/mouse/day CMX, B: 1.5 mg/mouse/day CMX, C: control) from 7 weeks of age. Animals were followed up for evaluation of diabetes incidence up to 32 weeks of age. There was a tendency for a delayed onset of hyperglycemia in mice of group B up to 26 weeks of age; however no significant difference in the cumulative incidence of diabetes at 32 weeks of age was observed (A: 57.5%, B: 38.5%, C: 38.5%). No differences were found in the number of infiltrated islets in animals culled at 10 weeks of age treated with CMX from 4 weeks of age. We conclude that CMX does not modify the course of insulitis and diabetes incidence in NOD mice although though the appearance of glycosuria was delayed by this treatment.

Adjuvants, Immunologic↗
PubMed1992

A radiopharmaceutical for imaging areas of lymphocytic infiltration: 123I-interleukin-2. Labelling procedure and animal studies.

The labelling of interleukin-2 (IL-2) with 123I and its in vivo application for imaging chronic pathological lymphocytic infiltrations are described. The lactoperoxidase/glucoseoxidase technique was the labelling method of choice leading to immunoreactive IL-2 with high specific activity. Labelled IL-2 was injected in diabetes-prone non-obese diabetic (NOD) mice with pancreatic lymphocytic infiltration. As control animals, Balb/c mice were used. As specificity control, monoclonal antibodies AMT13 and UCHT1, bovine serum albumin and alpha-lactalbumin were radioiodinated and injected in mice. Eighteen NOD mice and four control Balb/c mice were used for gamma camera imaging experiments. Fifty-four NOD and 20 Balb/c mice were used for time course single organ counting and autoradiography. Gamma camera images showed that radioactivity accumulated in the pancreatic region from the 10th minute onwards in NOD mice injected with 123I-IL-2 but not in Balb/c mice, or in NOD mice injected with control radiopharmaceuticals. These findings were confirmed by counting the radioactivity present in single organs. Autoradiography of NOD pancreas, after injection of labelled IL-2, showed that radioactivity was specifically associated with infiltrating lymphocytes. In conclusion, this technique is highly specific and easy to perform and we suggest its application in humans for in vivo detection of areas of lymphocytic infiltration.

Animals↗
PubMed1990

Raised temperature reduces the incidence of diabetes in the NOD mouse.

An association between the incidence of childhood Type 1 (insulin-dependent) diabetes mellitus and the average yearly temperature in different countries has been reported, the incidence being higher in countries with a lower mean temperature. We have studied the effect of environmental temperature on the incidence of diabetes in an animal model of Type 1 diabetes, the non-obese diabetic (NOD) mouse. Female NOD mice were divided at weaning, with one group placed at a higher temperature (mean 23.7 +/- 1.7 degrees C) and the other at a lower temperature (21.0 +/- 1.8 degrees C). At 20 weeks of age 6 of 16 mice at lower temperature and 1 of 17 mice at higher temperature had developed diabetes (p less than 0.02); at 30 weeks 10 of 16 and 5 of 17 mice had developed diabetes (p less than 0.05). Non-diabetic animals in the low temperature group had a higher food intake than those in the high temperature group between 13-15 weeks of age (28.0 +/- 1.2 g/week vs 24.8 +/- 0.7 g/week, p less than 0.05). In a parallel experiment, histological examination showed that there were similar degrees of insulitis in the high and low temperature groups at seven weeks of age. We conclude that environmental temperature can affect the incidence of diabetes in the NOD mouse and that this may be related to alterations in food intake.

Animals↗
PubMed1990

Can iodine-131 whole-body scan be replaced by thyroglobulin measurement in the post-surgical follow-up of differentiated thyroid carcinoma?

This study compared serum thyroglobulin measurement and whole-body scans in the post-surgical follow-up of patients with differentiated thyroid carcinoma. Thyroglobulin levels were measured in 61 patients receiving L-thyroxine therapy after thyroidectomy, and again after suspension of therapy, before performing a whole-body scan with iodine-131. The sensitivity, specificity, and accuracy of thyroglobulin levels, measured during L-thyroxine therapy, for diagnosis of tumor residue or metastases were then calculated and compared with results obtained by diagnostic whole-body scanning. Our data show that neither thyroglobulin levels nor whole-body scans alone can discriminate between patients with or without metastases. Sensitivity reached 95.7%, specificity 100%, and accuracy 96.7% if results of both procedures were also taken into consideration. We conclude that in the management and follow-up of patients with differentiated thyroid carcinoma both parameters need to be evaluated.

Adenocarcinoma↗
PubMed1989

The natural history of lymphocyte subsets infiltrating the pancreas of NOD mice.

A longitudinal study of lymphocytic infiltration in the endocrine pancreas of non-obese diabetic mice was performed to investigate the role of different lymphocyte subsets in the pathogenesis of diabetes. The incidence of insulitis and the percentage of mononuclear cell subsets in the pancreas were evaluated in non-obese diabetic mice of various ages (5, 9, 13, 17, 22, 29 and 36 weeks). Cryostat sections of pancreas were stained with heamatoxilin-eosin or with different monoclonal antibodies against total T lymphocytes, helper T lymphocytes, cytotoxic/suppressor T lymphocytes, activated interleukin 2 receptor positive lymphocytes and B lymphocytes. A monoclonal antibody against Class-II antigens was also used. Positive cells were revealed by the immunoperoxidase technique. Insulitis was found in 5 weeks old mice but to a lesser extent than in adult animals. No significant variation between infiltrating cell subsets was found in different age groups. T lymphocytes ranged between 20.4% and 28.1%, B lymphocytes between 28.8% and 30.8% and Class-II positive cells between 22.8% and 32.2%. Interleukin 2 receptor positive cells ranged between 5.5% and 8.5% as detected with AMT-13 monoclonal antibody which recognise the interleukin 2 binding site. A higher percentage of activated cells was observed using another monoclonal antibody (7D4) directed against a different epitope of the interleukin 2 receptor, suggesting the presence of activated lymphocytes with interleukin 2 receptors saturated by interleukin 2. No insulin-containing cells were found to express Class-II molecules as demonstrated by a double immunofluorescence technique. Most infiltrating mononuclear cells were found to be positive for Class-II and L3T4 antigens or to be Class-II positive and express surface immunoglobulins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Lessons from the NOD mouse for the pathogenesis and immunotherapy of human type 1 (insulin-dependent) diabetes mellitus.

Suitable animal models of human Type 1 (insulin-dependent) diabetes mellitus have long been sought, in particular a model that would permit detailed histological and immunological investigation of changes in the islet preceding the metabolic disorder. This would allow hypotheses as to pathogenesis of the condition to be examined and interventions such as immunotherapy to be tested. The most widely studied models include the low-dose streptozotocin induced diabetic mouse and the BB rat, but both differ in important respects from the human disease. In this review we describe one highly successful model, the non obese diabetic mouse. Selected aspects of pathogenesis and immunotherapy are presented and analogies with human Type 1 diabetes discussed.

Animals↗
PubMed1987

Detection of activated lymphocytes in endocrine pancreas of BB/W rats by injection of 123I-interleukin-2: an early sign of type 1 diabetes.

Recombinant interleukin-2 (IL2) was labelled with iodine-123 by a modified chloramine T method. The labelled IL2, which had a high specific activity (100-150 microCi/microgram) and retained its capacity for binding to the IL2 receptor on activated lymphocytes in vitro, was injected intravenously into BB/W diabetes-prone and normal rats. Combined immunoperoxidase staining and autoradiography of organ sections revealed that labelled IL2 bound specifically in vivo to IL2-receptor-positive cells in the spleen of both normal and BB/W rats and to activated lymphocytes infiltrating the pancreas of BB/W rats. The severity of lymphocytic infiltration correlated with the degree of radioactivity in the pancreas of BB/W rats. Time-activity curves, generated over organs of injected rats after gamma camera imaging, confirmed that radioactivity was greater in the pancreas of diabetes-prone than in normal rats. 123I is a suitable isotope for gamma camera imaging, so the intravenous injection of IL2 labelled with iodine-123 may be valuable for the in-vivo visualisation of activated lymphocytes in tissues infiltrated by lymphocytes.

Animals↗