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Biomedical subjects

S Iannelli

Publications and source records attributed to S Iannelli.

At least 19 recordsLinked to original sources

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

Antibodies

The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies.

Posttransplant monitoring of anti-HLA antibodies with routine techniques gives unsatisfactory results due to a variety of technical limitations. We investigated how a new alternative technique correlates with posttransplant clinical events. A total of 313 nonselected serum samples from 136 patients were screened by an ELISA utilizing captured soluble HLA class I antigens. We observed the absence of anti-HLA antibody production in acute rejection cases responding to standard antirejection therapy. On the other hand, we showed a clear presence of these antibodies in acute rejection episodes not responding to standard therapy (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine posttransplant monitoring by ELISA offers early risk assessment that is crucial for proper immunosuppression and for antirejection therapy choice.

Cytotoxicity, Immunologic

A 3D study of intra and extracellular structures of liver in beta-thalassemia intermedia: an OsO4 maceration analysis.

A scanning electron microscopy study of liver changes has been carried out in three patients affected by beta-thalassemia intermedia (BTI). Applying a new osmium maceration method, recently developed in our laboratory, we had the opportunity to obtain, at SEM, tridimensional images of intra and extracellular structures. Other than the previously reported lesions in BTI, we observed the following pathological findings: disarrangement of the cell structure by a high number of hemosiderin loaded lysosomes; alterations in shape and in diameter of the nuclear pores; presence of apoptotic bodies scattered among the parenchymal cells; deposition of collagen fibers in the space of Disse to form a perihepatocytic dam; enlargement of the sinusoidal endothelial cell fenestrae of the sieve plate. By complete digestion of liver cells, we evidenced a diffuse pericellular fibrosis, made up of interlacing fibrils. Our study evidences some not yet reported morphological lesions in BT. Since patients affected by BTI do not need blood transfusions, these lesions could be considered intrinsic of the disease.

Adult

ELISA anti-HLA antibody screening identifies non-complement-fixing antibodies responsible for acute graft rejection. A case report.

We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.

Adult

Uneven hepatic iron and phosphorus distribution in beta-thalassemia.

BACKGROUND/AIMS: Determination of hepatic iron concentration is crucial in the evaluation of iron-storage disease. Iron content is normally determined in a part of a needle liver biopsy and the value obtained is considered to be representative of the iron concentration in the whole liver. To evaluate the reliability of this procedure, we studied iron distribution in the liver of two beta-thalassemic patients. Since the transport of intracellular iron is mediated by phosphates, we also studied the hepatic phosphorus distribution. METHODS: At autopsy, a liver slice extending from the left to the right lobe was divided into 51 and 49 samples, respectively. Each specimen was subdivided into two parts: one of them was paraffin-embedded and utilized for the histochemical detection of iron; the second part was analyzed for iron and phosphorus content by induced coupled plasma atomic emission spectroscopy. RESULTS: The histological picture of both livers was characterized by portal and periportal fibrosis associated with iron storage of different degree, without cirrhosis. The mean iron concentration of the liver was 20,631 +/- 4903 micrograms per g of dry tissue (micrograms/g dt) and 13,901 +/- 1976 micrograms/g dt, respectively. A striking variability in iron content between samples was also found: iron concentration ranged from 11,537 to 32,347 micrograms/g dt in the first case and from 6257 to 16,493 in the second case. We even observed regional differences in iron concentration, with a preferential peripheral accumulation in both cases and a tendency of the left compartment of the liver to accumulate more iron in the first case. Histochemical analyses confirmed the uneven iron distribution even at the acinar level, showing iron mainly being stored in hepatocytes and Kupffer cells of zone 1 of the acinus, with decreasing amounts of iron in zones 2 and 3. The mean hepatic phosphorus concentration was 6662 +/- 1300 micrograms/g dt (range: 4348-9947) and 7502 +/- 986 micrograms/g dt (range: 5844-90,282), respectively. The regional distribution of phosphorus was similar to that observed for iron. A strict correlation between iron and phosphorus content was also observed. CONCLUSIONS: Our data show that: 1) iron and phosphorus are unevenly distributed in the beta-thalassemic liver, even in the non-cirrhotic stages; 2) a regional pattern of iron and phosphorus distribution is evident, characterized by higher concentrations at the periphery of the liver; 3) the observed uneven distribution of iron and phosphorus implies that their content determined in a small liver sample cannot be considered as absolutely representative of the mean hepatic iron concentration. Therefore, iron concentrations determined in a part of a needle liver biopsy should be interpreted with caution in monitoring the efficacy of the iron-chelating therapy in beta-thalassemic patients.

Adult

Fibroblast proliferation over dialysis membrane: an experimental model for "tissue" biocompatibility evaluation.

The present study reports on a biological model based on fibroblast proliferation applied to 3 different types of flat-plate dialysis membrane, in order to ascertain whether the artificial materials currently used in hemodialysis cause in vitro cellular proliferation. The study plan we followed involved plate membrane isolation from non-used dialyzers and used dialyzers, observed through scanning electron microscopy (SEM) both before and after testing with human fibroblasts by means of cell culture. Fibroblast growth was assessed by phase contrast light microscopy examination and cytometric DNA content evaluation. Our investigations proved that the artificial materials we considered interact with fibroblast cultures. Noticeable proliferative response was observed both after contact with unused material and on mediation by the protein layer absorbed on the membrane surface at the end of dialysis sessions. In this last case fibroblast proliferative activity appeared higher than that observed with unused membranes, showing that the soluble molecules entrapped in the protein layer appeared able to exert a biological activity even in vitro tests.

Acrylic Resins

Immunologic changes in circulating leukocytes in the presence of atherosclerotic disease.

To assess the numeric and functional changes in circulating white blood cells in the presence of severe atherosclerosis, 25 subjects with marked, angiographically assessed, atherosclerotic lesions and 29 selected controls were studied. Of the differential leukocyte counts, only monocyte count was significantly higher in the atherosclerotic than in the control subjects (449.0 +/- 115.6 (1 S.D.) vs. 344.1 +/- 138.8/mmc; P = 0.0016). By flow-cytometry no significant differences concerning monocyte surface antigens were found, except a feeble decrease in beta 2-microglobulin in the atherosclerotic subjects. As to lymphocytes, an increase in the CD8 population (33.4 +/- 6.8 vs 28.6 +/- 6.5%; P = 0.0144) and decreases in class I HLA antigen (96.6 +/- 7.3 vs 99.4 +/- 0.7%; P = 0.0049), beta 2-microglobulin (97.9 +/- 2.1 vs 99.3 +/- 1.0%; P = 0.0055) and especially in vivo DNA synthesis (3.8 +/- 1.2 vs 5.3 +/- 2.1%; P = 0.0102) percent expressions were found in the atherosclerotic patients with respect to the controls. This study shows that circulating monocytes are increased in atherosclerotic disease, possibly due to their participation in the phagocytosis of lipids in the arterial wall, with no further immunologic involvement. Conversely, the replicative activity of T lymphocytes is decreased, which might be a consequence of or a factor predisposing to atherosclerosis.

Acute Disease

Validity of flow cytometry for cross-match evaluation in clinical renal transplantation.

This paper reports a 2-year experience of more than 5,000 cross-match tests for renal transplantation. Tests were performed by means of both standard light microscopy and an innovatory method based on flow cytometry, an up-to-date investigative technique for computerized analysis of individual cell characteristics. Flow cytometry allowed a better detection of weak positive reactions (false-negative cross-matches) than light microscopy, thus reducing the risk of selecting candidates with donor presensitization. Transplant clinical outcome supported the value of this original and advanced technological method.

Antibodies

Cellular immunology in regular dialysis: a biological model for biocompatibility evaluation.

Cellular immunity represents an interesting biological model for biocompatibility evaluation of artificial materials owing to its sensitivity to contact with the external environment and its capability of modulating response reactions to foreign agents. Advanced methodologies such as flow cytometry and the immunoenzyme techniques in particular have given new insights into lymphocyte structure and functions, enabling analysis of the in vivo modification of these cells. By means of these sophisticated techniques we investigated lymphocyte activation and proliferation during one single haemodialysis session. Findings clearly show that increases in HLA antigen density (class I and II), DNA synthesis, and interleukin-2 receptor serum concentration (Il-2R) take place during the dialysis procedure, and reach their maximum during the first hour of extracorporeal circulation. The relationship between dialysis procedure and cellular immunity appears noticeable and is of potential value in the evaluation and quantification of the biocompatibility of different dialysis membranes.

Adult

[Collateral effects of 9-alpha-fluor-prednisolone acetate and kanamycin, administered by nasal spray. Clinical experience and experimental data].

Iatrogenic pathology due to treatment with steroid drugs used by systemic route is well known. On the contrary iatrogenic pathology due to topical use of these drugs is rarely reported. Two cases of abuse of 9-alpha- fluor-prednisolone and kanamycin administered by endonasal route are reported. The same treatment has been carried out in patients and rabbits. Clinical and bio-humoral data in patients and anatomo-pathological findings in rabbits are reported. The risks, sometimes underestimated, of an overdose of corticosteroid and antibiotic drugs used by endonasal route are pointed out.

Administration, Inhalation

Biocompatibility of charcoal hemoperfusion. Effects of long-term treatment on lymphocyte characteristics and function.

Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.

Antigens, Surface