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Biomedical subjects

P Pozzilli

Publications and source records attributed to P Pozzilli.

At least 181 records · Page 10Linked to original sources
PubMed1989

Thymopentin induces release of ACTH-like immunoreactivity by human lymphocytes.

Peripheral mononuclear (PMN) cells are known to produce ACTH-like immunoreactivity (ACTH-LIR) in vitro. Based on these findings the aim of this study was to find out whether thymopentin (the active pentapeptide of the native hormone thymopoietin) may stimulate ACTH-LIR production and release by cultured normal human lymphocytes. Thymopentin at concentration of 1 microgram/ml was capable of inducing ACTH-LIR release by normal human PMN cells (median 22 pg/ml) whereas ACTH-LIR inside cells was lower (median 11 pg/10(7) cells). The chromatographic characterization of the eluted material identified the presence of ACTH immunoreactive peptides with the elution characteristics of the precursors 31 K proopiomelanocortin, 22 K ACTH and 4.5 K ACTH, together with higher molecular weight material (greater than 43 K). These data demonstrate that thymopentin induces ACTH-LIR release by human lymphocytes, thus adding a novel factor to those already reported (corticotrophin releasing factor, lipopolysaccharide, viruses) capable of such function.

Adrenocorticotropic Hormone↗
PubMed1988

Quantitative immunological differences between newly diagnosed Graves' disease patients and relapsed patients.

Class 2-positive T cells, T-cell and mononuclear cell subsets, thyrotropin receptor antibodies (TRAb) and immune complexes were evaluated in 34 newly diagnosed Graves' patients and in 13 relapsed patients before a cycle of specific medical treatment. Class II-positive T lymphocytes were detected by monoclonal antibodies against different epitopes of class II antigens, whereas 4F2-positive cells were detected by 4F2 monoclonal antibody. 4F2-positive cells were statistically increased in newly diagnosed Graves' patients compared to relapsed patients (p less than 0.05). An increased percentage of class II activated T cells, detected by monoclonal antibodies L243, was found in newly diagnosed patients in comparison with relapsed subjects (p less than 0.025). Newly diagnosed Graves' patients showed a significant decrease in the ratio suppressor/cytotoxic T cells in comparison with normal control subjects but not with relapsed patients. Ninety-one % of newly diagnosed Graves' patients showed a high TRAb value, whereas only 69% of relapsed patients showed increased values (p less than 0.025). No difference was observed in the immune complex positivity between newly diagnosed Graves' patients and relapsed subjects. In conclusion, both humoral and cellular immune differences were found in relapsed patients vs newly diagnosed Graves' patients. The immunological abnormalities are quantitatively more pronounced in the latter group.

Adolescent↗
PubMed1988

Inhibition of protein non-enzymic glycation induced by Bendazac.

Enhanced non-enzymic glycation of proteins has been suggested to play a role in the pathogenesis of diabetic microangiopathy. Thus pharmacological inhibition of this reaction could be envisaged to delay the development of late diabetic complications. In the present study we have investigated the effect of a new compound, 1-Benzylindazole-3-oxyacetic acid, Bendazac (BDZ) on the in vitro glycation of soluble proteins (albumin and fibrinogen) and isolated glomerular basement membrane (GBM). The data obtained indicate that BDZ is capable of reducing significantly the glycation of albumin and fibrinogen (p less than 0.001). When present in concentrations usually found in patients undergoing therapy (40-80 micrograms/ml), an inhibitory effect on soluble proteins was also observed. Inhibition of glycation of GBM was found only in the presence of the active metabolite (5 hydroxy BDZ) and at high glucose concentrations. These results suggest that BDZ could interfere with protein non-enzymic glycation and its use in patients with diabetes may be then taken into consideration to evaluate the effect on late diabetic complications.

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↗
PubMed1987

Class-II and IL2 receptor positive cells in the pancreas of NOD mice.

The aberrant expression of Class-II molecules on pancreatic B cells in Type 1 (insulin-dependent) diabetes is still a matter of debate. In order to verify if Class-II molecules are expressed on islet cells in the NOD mouse we have studied 21 female mice of different ages (5 to 22 weeks). Serial cryostat pancreas sections were stained with monoclonal rat antibodies against Class-II antigens (P7/7) and the IL2 receptor (AMT-13). Our results show no Class-II expression by endocrine cells at any age, whereas about 25-32% of mononuclear cells infiltrating the islets were Class-II positive, and only 6-9% were IL2 receptor positive. No staining, except of occasional tissue macrophages, was observed in the pancreas of BALB/c, CBA or B10.SCSN mice. Our data are in contrast with those recently published and therefore the reality of expression of Class-II molecules by islet cells of NOD mice should be viewed with caution.

Animals↗
PubMed1987

Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes.

Twenty patients with well controlled Type 1 (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb). The median rise of HbsAb titres was 230 mIU/ml in normal subjects and 50 mIU/ml in diabetic patients (p less than 0.001). Eight patients (40%) failed to reach HbsAb titres above 30 mIU/ml, the level considered to give optimal protection against the infection, whereas only one normal control subject failed to reach this level. Five patients (25%) showed no response despite a fourth dose of the vaccine. There was an increased frequency of HLA-DR7 in low responders and a decreased (less than 1.5) helper/suppressor lymphocyte ratio. Diabetic patients are thus less likely to mount a protective antibody response following vaccination against hepatitis. Since hepatitis B surface antigen is reported to be considerably more common in diabetic patients than control subjects, infection with hepatitis B virus may have a greater risk of chronicity in diabetes.

Adult↗
PubMed1987

Labelling of interleukin-2 (IL-2) with 123-iodine with retention of its capacity to bind to activated lymphocytes.

Human recombinant interleukin-2 (IL-2) was labelled with Iodine-123 using modified Bolton and Hunter method. Separation from free iodine was performed by gel filtration chromatography using a Sephadex G10 column. HPLC analysis of labelled IL-2 showed that 98% of TCA precipitable radioactivity eluted in a single peak. The immunoreactivity of 123I-labelled IL-2 was determined by divert binding using the Fluorescence Activated Cell Sorter (FACS) and by receptor binding assay of IL-2 to activated lymphocytes. To demonstrate in vivo binding to activated lymphocytes, 123I-labelled IL-2 was injected intravenously into a newly diagnosed diabetic BB/Wistar rat. Higher radioactivity was detected in the pancreas and in the lymph nodes of the BB/W rat compared to a normal rat. These preliminary data show that 123I-labelled IL-2 retains its immunoreactivity and capacity to bind to activated lymphocytes both in vitro and in vivo and may be used for in vivo localization of lymphocytic infiltration in Type 1 diabetes.

Animals↗
PubMed1987

In vivo kinetics of 123I-labelled insulin: studies in normal subjects and patients with diabetes mellitus.

Radioactive tracer techniques using 131I- and 125I-insulin have been applied to study insulin metabolism. A simple method to label human insulin with 123I to a high specific activity is described. We have used this radiotracer to study insulin kinetics in vivo in normal subjects and in two groups of diabetic patients. The rate of decline in plasma radioactivity was shown to be significantly reduced in patients with diabetes. There were no significant differences in the time-activity profiles of liver and kidneys between the groups studied. This technique may provide insight into the mechanism of some forms of insulin resistance.

Adult↗
PubMed1987

Activation of peripheral blood and intestinal lamina propria lymphocytes in Crohn's disease. In vivo state of activation and in vitro response to stimulation as defined by the expression of early activation antigens.

In the present study the state of activation of either peripheral blood and intestinal lamina propria mononuclear cells in Crohn's disease was defined by investigating the expression of early activation antigens (namely the 4F2 antigen, the transferrin receptor and the interleukin-2 receptor). The expression of 4F2 and T9 antigens was greatly increased--in the peripheral blood and in the intestinal lamina propria whereas the proportion of interleukin-2 receptor bearing cells was much less pronounced. The counts of early activation antigens bearing cells in the lamina propria were quite comparable with those of the autologous peripheral cells. In the peripheral blood counts of 4F2 and T9 positive cells were very high in patients with active Crohn's disease but patients with quiescent disease also had a significantly raised proportion of 4F2 and T9 bearing cells. Only in those patients with no evidence of macroscopic disease (namely those resected without recurrence) the counts of early activation antigens bearing cells were within the normal range. The in vitro mitogen induced expression of early activation antigens on either peripheral and intestinal mononuclear cells of patients with Crohn's disease proved to be both quantitatively and qualitatively similar to that of the controls showing the full expression of 4F2, transferrin receptor, and interleukin-2 receptor. While demonstrating that in Crohn's disease there was no intrinsic defect of generation and expression of growth factors receptors by peripheral and intestinal lymphocytes, these results showed that there was a divergence in the expression of early activation antigens in vivo and in vitro. This would indicate that in Crohn's disease there is an in vivo increased population of preactivated rather than fully activated lymphocytes consisting of 4F2 and T9 bearing cells. The high proportion of these cells in the peripheral blood and in the intestine suggests that a chronic immune activation is present in these patients outside as well as within the affected bowel.

Adult↗
PubMed1987

Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin.

A double blind study with thymopentin (TP5) and placebo was performed in 49 patients affected by Type 1 and Type 2 diabetes of long duration characterized by a reduction of the CD4/CD8 (helper/suppressor) lymphocyte ratio. TP5 (50 mg) was administered subcutaneously 3 times weekly for 1 month. Total peripheral lymphocytes and functionally different cell subsets were measured throughout the course of the study. Data showed a statistically significant increase of the CD4/CD8 lymphocyte ratio (p less than 0.02) and of the percentage of B lymphocytes (p less than 0.001) only in the TP5 receiving group. No side effects were observed during the study and patients remained well controlled. These results suggests that TP5 may be administered safely to diabetic patients and by improving impaired cell mediated immune parameters TP5 may contribute to prevent the development of infections in these patients.

Adult↗
PubMed1987

In vivo determination of cell mediated immune response in diabetic patients using a multiple intradermal antigen dispenser.

The in vivo cell mediated immune response using a multiple intradermal antigen dispenser (Multitest) was evaluated in 99 diabetic patients (24 Type I and 75 Type II) and in 50 age matched normal subjects. Seven different antigens (tetanus, diphteria, streptococcus, tubercoline, candida, trichophyton, proteus and a glycerine control) were applied in the forearm and the induration for the antigens tested was measured 48 hours later. A score was calculated adding the arithmetic means obtained with each single antigen. Overall we did not find major differences between diabetic patients and controls except Type I patients of shorter duration (less than 5 years) having a reduced response (p less than 0.05) and both Type I and Type II patients showing an elevated response to candida antigen (p less than 0.001). No correlation was found between the intradermal response and metabolic control. As the intradermal test is a model for delayed type of hypersensitivity, these data suggest that the in vivo lymphocyte to lymphocyte cooperation in patients with long standing diabetes is not impaired.

Adult↗
PubMed1987

Ultrastructure of lymphocyte subsets and of activated lymphocytes in type 1 diabetes as defined by monoclonal antibodies and the immunogold technique.

The ultrastructure of peripheral blood lymphocyte subsets and activated lymphocytes from 5 patients with recent onset insulin-dependent diabetes as identified by monoclonal antibodies (CD4, CD8 and 4F2) and labelled with gold coupled goat anti-mouse IgG are described and depicted. Electron microscopy revealed no differences in appearance between investigated lymphocyte subsets at the single cell level. Activated lymphocytes as defined by an early activation antigen (4F2) do not always have a characteristic appearance nor do they show morphological signs of activation in all cases. We would conclude that it is not possible to recognize different lymphocyte subsets based only on their ultrastructure.

Antibodies, Monoclonal↗
PubMed1986

The immune response to influenza vaccination in diabetic patients.

The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR) anti-influenza vaccine recommended by WHO. The antibody titre and the cell-mediated immune response to the 3 virus strains, as evaluated by the generation of activated lymphocytes and enumeration of B lymphocytes, were studied before and 18 h, 72 h and 1, 2, 3 and 6 weeks after vaccination. Overall, the humoral and cell-mediated immune responses were normal in both groups of patients. However, patients with Type 1 diabetes showed a statistically significant increase (p less than 0.01) of antibody titre of the A/Chile and an increased percentage of B lymphocytes one week after vaccination compared to age-matched control subjects. Four out of 21 patients with Type 2 diabetes had no antibody response to all 3 virus strains. A significant reduction (p less than 0.01) of the percentage of activated cells possessing receptors for interleukin-2 was observed 72 h after vaccination in patients with Type 2 diabetes compared to age-matched control subjects. None of the patients who received the vaccine developed influenza in the course of the following year. These results suggest that valid protection against the influenza virus can be obtained in patients with Type 1 and Type 2 diabetes.

Adult↗