Biomedical subjects
Publications and source records attributed to M Mancuso.
A case of Hb Shepherds Bush observed in a Sicilian family is reported. The iron status has been evaluated since chronic haemolysis may cause hemosiderosis. The paper also refers to the diagnostic workout for all chronic hemolytic anemias.
Humoral and cellular immune factors were studied in 33 newly diagnosed Graves' patients at diagnosis and in 12 of these patients at regular intervals thereafter. All the patients were treated with carbimazole for 15 months (initially 60 mg and then 20 mg supplemented with L-Thyroxine). The incidence of relapse after treatment was 42%. Thyrotropin receptor antibodies (TRAb), T-cell subsets, K and NK cells and mononuclear cells expressing surface antigen markers of different activation were evaluated respectively by the use of a radioimmunoassay and a panel of monoclonal antibodies. Patients in the follow-up study were HLA-A, B, C and D typed. TRAb levels (91%) and levels of 4F2-positive cells (73%) and class II-positive lymphocytes (69.6%) were significantly increased in newly diagnosed Graves' patients in comparison with normal controls, whereas CD8 cells were significantly decreased. There was a significant inverse correlation between the increase in 4F2-positive cells and TRAb values. In the follow-up study both humoral and cellular immunological parameters showed a wide variation in levels, but TRAb, 4F2 and L243 values declined on average with respect to diagnosis. After 15 months some patients still showed abnormal values of activated T cells and TRAb values. All patients who relapsed (42%) after medical treatment showed a significant increase of 4F2-positive cells, and some of TRAb, some time before the appearance of clinical symptoms. Finally, no correlation was found between HLA type and relapse of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
The chronic hyperglycemia in diabetes mellitus enhances the nonenzymic glycation of structural proteins possibly increasing the formation of highly reactive advanced glycation end products (AGE). These protein changes might be involved in tissue-damaging mechanisms leading to diabetic complications, including diabetic nephropathy. To simulate these events, an in vitro model, based on isolated human glomerular basement membrane (hGBM), has been developed. In this study we have investigated the extent of AGE formation and the binding changes induced by the nonenzymic glycation of hGBM. An enriched fraction of hGBM was isolated from normal human kidneys and glycated in vitro by incubation with glucose (500 mmol/l) at 37 degrees C for 10 days. The presence of AGE was investigated by two methods - spectrofluorescence and the diazonium salt reaction - both specific for this type of chemical entity. The binding capacity of glycated hGBM was tested by a 10-day incubation with human insulin, albumin, immunoglobulin G and fibrinogen. Higher relative spectrofluorescence values at 440 nm emission (20.0 +/- 2.0 vs. 12.5 +/- 5.0) and higher absorbance values at 492 nm (0.798 +/- 0.063 vs. 0.429 +/- 0.228) indicated the presence of increased levels of AGE in glycated vs. native hGBM. Insulin and the three proteins were bound to hGBM in increased amounts after its glycation (p less than 0.05). The results obtained in this in vitro model confirm that enhanced nonenzymic glycation of hGBM induces the formation of AGE and possibly, through these compounds, alters its physicochemical and binding properties. This reaction might contribute to the mechanisms eventually leading to diabetic nephropathy.
The CT, surgical and histological findings were examined of 350 lymph nodes in a perspective study of 50 patients affected with lung cancer. CT accuracy could thus be evaluated in assessing the size of hilar and mediastinal lymph nodes; the incidence of histologically-proven metastases in nodes more/less than 10 cm in diameter could also be determined, together with CT diagnostic accuracy for nodal metastases. Finally, CT capabilities were also evaluated in distinguishing N0 from N1-N2 patients. CT proved to have high negative predictive value and low positive predictive value, which caused the authors to raise the normal threshold value of CT evaluation of the greatest diameter for hilo-mediastinal nodes from 10 to 20 mm.
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In search of a marker for monitoring the progression of diabetic nephropathy from the stage of charge- to that of size-selectivity loss, attention has been focused on the evaluation of immunoglobulin G (IgG) subclasses in the urine. We have developed a new sensitive enzyme immunoassay for the quantitation of urinary IgG1 and IgG4. Mouse monoclonal antibodies specific for each subclass were bound to microtitre wells precoated with rabbit anti-mouse immunoglobulin antibody. IgG1 and IgG4 of standard preparations (or of samples to be tested) were revealed using peroxidase-conjugated rabbit anti-human IgG. The procedure was carried out at 4 degrees C. This method can detect about 2 ng/ml of IgG4 and 20 ng/ml of IgG1. The monoclonal antibodies used were shown to be highly subclass-specific. IgG1 and IgG4 have a similar molecular weight but a different pH (about 9 and 4.6 respectively); a change in their ratio in the urine of diabetic patients may indicate a progressive deterioration of kidney function at the stage of incipient diabetic nephropathy.
Data (radiological, endoscopic, histological, clinical and surgical) are presented on 21 subjects with pulmonary carcinoid tumour encountered in the Turin University Chest Surgery Centre in 1980-1985. All patients were subjected to fibrobronchoscopy which revealed the tumour in 18 cases (14 were given multiple biopsies and in 4 cases samples could not be taken due to the patient's intolerance of the endoscopic manoeuvre). No appreciable bleeding occurred after any biopsy. Surgery was performed on all 21 patients (2 pneumonectomies, 7 bilobectomies, 12 lobectomies). There was 85.71% correspondence between pre and post-operative histological diagnosis.
The value of serum ferritin assays in the diagnosis and staging of non-microcytoma bronchial cancer is assessed. It is pointed out that the marker is only minimally specific and sensitive in the diagnostic phase as well as being only slightly indicative in the staging of NSCLC.
One hundred sixty-five patients with surgically treated thymoma were followed over 28 years; 73% had myasthenia gravis at presentation. Invasiveness was based on macroscopic findings at operation. Postsurgical radiotherapy or chemotherapy were not routinely used. Overall survival was 84%, 79%, and 65% at 3, 5, and 10 years, respectively. Patients with invasive thymoma survived for a shorter period than patients with noninvasive tumors (67% versus 85% at 5 years); when radical excision was possible, no difference was detectable between the two groups. Patients with subtotally resected or only biopsied invasive thymomas survived 59% and 42% at 5 years, respectively. Lymphoepithelial cases had the worst prognosis of the histologic types considered. Myasthenia gravis did not adversely affect survival. Surgery is the basic treatment of thymomas. Macroscopic invasiveness and degree of excision judged by the surgeon have prognostic value and are reliable criteria of malignancy. Radiotherapy and chemotherapy may be effective, but their use should be limited to controlled trials.
Serum levels of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were investigated in 53 lung cancer patients. The higher percentage of patients with serum CEA positivity was observed within the anaplastic lung cancer group. TPA serum positivity was found in similar percentage in all the examined groups. Relationship between serum CEA positivity and/or serum TPA positivity and survival were then carried out.
The detection of microalbuminuria has a high prognostic value in diabetic patients with no symptoms of clinical nephropathy. Attention has been focused on the development of a simple, reproducible, specific, and, above all, sensitive method to detect albuminuria in the urine. The method is based on the competitive binding between albumin in the urine to be tested and a fixed amount of radiolabelled albumin to anti-albumin immunoglobulins in solid phase. The immunoglobulin C fraction of a rabbit anti-human albumin antiserum was left to coat highly adsorbent polystyrene microtitre tubes. While the aspecific tube binding was overcome by saturation with a solution of gelatine, increasing dilutions of standard albumin or the diluted urine samples to be tested were left to incubate with an equal volume of radiolabelled albumin at room temperature for 1 hour. The cold/hot albumin mixture was added to anti-albumin immunoglobulin-coated tubes, which had been repeatedly washed, and left to incubate. After washing, radioactivity was assessed. This assay has proved to be fast, simple and highly sensitive since it detects up to 25 ng of albumin per ml and is of value in large-scale screening for microalbuminuria in diabetic patients.
The evaluation of both small amounts of urinary immunoglobulins and the albumin/immunoglobulin ratio are important indices during the early stages of diabetic nephropathy. For this reason there is at present a need for highly-sensitive and specific routine tests for urinary immunoglobulins. A technique has been designed based on the competition between radiolabelled immunoglobulin G and immunoglobulins in the urine to be tested in binding to an anti-immunoglobulin antibody in solid phase. The immunoglobulin fraction of a rabbit anti-human immunoglobulin antiserum in a basic Ca-carbonate buffer is left to coat highly adsorbent polystyrene microtitre tubes. After the antibody-coated tubes have been saturated with gelatine, a 1/5 dilution of the urine to be tested and an equal volume of purified and radiolabelled human immunoglobulin G are left to incubate and are then added to the antibody-coated tubes. After incubation and repeated washings, radioactivity is counted. This technique has the characteristics of a routine assay for the accurate detection of immunoglobulin G in the urine. It requires only a few microliters of urine, takes only 3 hr to complete (after having coated the tubes) and detects about 120 ng of immunoglobulin G/ml, well below what is needed to assess physiological or pathological values.
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Plasma levels of fibronectin were determined in 50 lung cancer patients and in 25 normal subjects. Immunoturbidimetric assay was performed to detect possible variations of plasma fibronectin concentration in neoplastic patients. Moreover plasma levels of fibronectin were related to clinical stage, histological type of tumor and survival after surgery.
Some aspects of the immunocompetent system are tested in 84 lung cancer patients at time of diagnosis and during the natural course of the disease. Results show no significant variations for many immunological tests during the course of the neoplasia. Significant alterations are observed in T-lymphocyte and macrophage evaluation. Moreover, some immunological data are related to lung cancer post-surgical survival.
Alpha and beta serum glycoprotein levels were determined in lung cancer patients at time of diagnosis and during the natural course of the disease. The results do not suggest that these glycoproteins can be used as tumour markers. Moreover, some glycoproteins, which have activity in cell-mediated processes and macrophage functions, can suggest prognosis.
Recent attempts implicating glycoproteins have been focused on the study of fibronectin. This glycoprotein was observed especially in cellular adhesivity processes. Some works were direct to detect the fibronectin concentration in plasma and in other biological fluids to relate increased or decreased levels in pathological features. In this paper we describe a study on plasma fibronectin in lung cancer patients during the course of the disease.