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Biomedical subjects

A Costantino

Publications and source records attributed to A Costantino.

At least 19 recordsLinked to original sources

Prevalence of hepatitis C virus antibodies in hemodialysis patients in the area of Milan.

We studied the seroprevalence of antibodies to hepatitis C virus (HCV Ab) in a cohort of 229 chronic hemodialysis patients followed by 6 Dialysis Units in the Milan area. HCV Ab was present in 51 (22.3%) of 229 examined patients. Previous blood transfusions and surgery did not clearly influence HCV seroconversion, whereas duration of dialysis treatment seems to be strictly related to HCV Ab positivity.

Adult

Identification and initial characterization of insulin receptor-like immunoreactivity in human plasma.

With a two-step purification procedure employing sequential affinity chromatography with insulin receptor monoclonal antibody followed by wheat germ agglutinin, we isolated from the plasma of two healthy individuals a material that reacted in a specific RIA for insulin receptors. This material produced dilution curves that were parallel to a human placental insulin receptor standard. This material also bound [125I]insulin; competition-inhibition curves revealed an ED50 of 0.3 nM, a value similar to that obtained with placental insulin receptors. The material purified from plasma was then labeled with [125I] Bolton-Hunter reagent, followed by polyacrylamide gel electrophoresis under reducing conditions and autoradiography. A band at 135 kilodaltons (kDa) was observed, corresponding to the alpha-subunit of the insulin receptor. Several bands ranging from 82-46 kDa were also detected. One or more of these fragments had intrinsic autophosphorylation activity, but only the 82-kDa band activity was responsive to insulin. In addition, employing the synthetic substrate poly(Glu4:Tyr1), no insulin-sensitive tyrosine kinase activity was present. These studies demonstrate, therefore, that insulin receptor-derived material is present in human plasma. This material retains high affinity insulin binding, but has an altered beta-subunit that is devoid of insulin-responsive tyrosine kinase activity.

Humans

Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas.

The receptor for Hepatocyte Growth Factor is a transmembrane tyrosine kinase encoded by the c-MET oncogene. We have previously shown that the Met protein is expressed in several human epithelial tissues. The receptor is barely detectable, however, in normal thyroids and in specimens from patients affected by non-neoplastic thyroid diseases. Now we report that the expression of the Met/HGF receptor is increased a hundred fold in 22 out of 41 human carcinomas derived from the thyroid follicular epithelium. A comprehensive analysis of 15 cases showed that the overexpressing carcinomas belong to histotype variants correlated with negative prognosis and in all but one case there were evidences of locally advanced disease and/or distant metastases. The 11 benign adenomas and the 5 medullary carcinomas tested were negative. Western blot analysis with monoclonal antibodies directed against either the intracellular or the extracellular receptor domains failed to reveal major structural alterations. Southern blot analysis also demonstrated that the c-MET gene was not amplified nor rearranged. These data suggest a role for the overexpression of c-MET oncogene in the pathogenesis and progression of thyroid tumors derived from the follicular epithelium.

Adolescent

Overexpression of insulin receptors in fibroblast and ovary cells induces a ligand-mediated transformed phenotype.

To investigate whether overexpression of the insulin receptor results in altered cell growth we used NIH 3T3 cells transfected with a bovine papilloma virus/insulin receptor cDNA construct (3T3/HIR). These cells expressed high numbers of insulin receptors (mean +/- sd, 631.0 +/- 16.7 ng receptors/10(6) cells). Insulin significantly stimulated the growth of 3T3/HIR cells maintained in serum-free medium. Moreover, in these cells, insulin induced marked phenotypic changes, including alterations in cell shape, loss of contact inhibition, and focal growth. In contrast to 3T3/HIR cells, insulin was without effect in either wild-type 3T3 cells (3T3/wt), 3T3 cells transfected with the neomycin resistance gene (3T3/NEO), or the bovine papilloma virus (3T3/BPV). To assess the presence of anchorage-independent growth, cells were seeded in soft agar and inspected for colony formation. 3T3/HIR cells showed absent or minimal colony growth in the absence of insulin. However, there was a dose-dependent insulin-stimulated increase in both colony size and number. Insulin-stimulated colony formation was specifically inhibited by an insulin antagonist, monoclonal antibody MA-10. In the presence of 100 nM insulin, about 3% of cells formed large colonies. Insulin neither stimulated growth nor induced colony formation in 3T3/wt cells or 3T3/NEO cells. Insulin also stimulated colony formation in CHO cells transfected with an insulin receptor cDNA construct. In conclusion, overexpression of normal insulin receptors induces a ligand-dependent transformed phenotype. This phenomenon may have clinical relevance by conferring a selective growth advantage to tumor cells with high numbers of insulin receptors.

Agar

Beta cell function, peripheral sensitivity to insulin and islet cell autoimmunity in cystic fibrosis patients with normal glucose tolerance.

Beta cell function, peripheral sensitivity to insulin and specific pancreatic autoimmunity were studied in 30 youngsters with cystic fibrosis (CF) accurately selected in order to fulfill the criteria for normal glucose tolerance. With respect to weight-matched controls, patients with CF exhibited a significantly lower glucose tolerance and a globally preserved, although delayed, insulin response to oral glucose tolerance test, while first-phase insulin secretion after i.v. glucose was blunted. Peripheral sensitivity to insulin, assessed in vivo by both the euglycemic clamp technique and the number of insulin receptors, directly measured in circulating monocytes, was superimposable in patients and controls. Serum islet-cell antibodies were not found in any of the patients. In conclusion, disorders of beta cell function may be observed in CF patients even when glucose tolerance is within the normal range. Such abnormalities are not associated with changes in peripheral sensitivity to insulin and do not seem to depend on specific autoimmune events.

Autoantibodies

Elevated insulin receptor content in human breast cancer.

The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0.95 + 0.68, P less than 0.001) and in six normal specimens obtained from reduction mammoplasty (0.84 +/- 0.78, P less than 0.001). The insulin receptor content in breast cancer tissues was also higher than in any normal tissue investigated including liver (Pezzino, V., V. Papa, V. Trischitta, A. Brunetti, P.A. Goodman, M.K. Treutelaar, J.A. Williams, B.A. Maddux, R. Vigneri, and I.D. Goldfine, 1989. Am. J. Physiol. 257:E451-457). The insulin receptor in breast cancer retained its ability to both bind insulin and undergo insulin-induced tyrosine kinase activation. Immunostaining of the specimens revealed that the insulin receptor was present in malignant epithelial cells, but was not detected in stromal and inflammatory cells. Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors.

Binding, Competitive

High prevalence of co-occurrence of anti-HCV and anti-HBc antibodies in chronic hepatitis patients from southern Italy.

The prevalence of anti-HCV and anti-HBV antibodies was investigated in a series of 77 adult patients with HBsAg negative, non autoimmune chronic liver disease. Anti-HCV were found in 68% and anti-HBc in 71% of the cases; 68% of the patients carried both antibodies. There was no difference in the proportion of anti-HBc positive cases between the anti-HCV positive or negative patients. The intense circulation of HBV infection in Southern Italy during the past decades might explain the high percentage of subjects with anti-HBc. Whether the co-occurrence of HCV and HBV infection may influence the natural history of the liver disease, remains to be established.

Adult

Dorsal midbrain syndrome in multiple sclerosis with magnetic resonance imaging correlation.

We describe the clinical characteristics and a series of magnetic resonance imaging (MRI) studies in a patient with the features of dorsal midbrain syndrome occurring in the setting of multiple sclerosis. A T2-weighted MRI study revealed a discrete abnormality in the tectum of the midbrain whereas a high volume delayed computed tomography (CT) scan was uninformative. In parallel with remission of the clinical findings, the MRI abnormality diminished over time and was no longer visible at one year suggesting that some MRI detected MS lesions can completely disappear with time. This report demonstrates the use of MRI to detect and to follow sequentially sites of known disease activity in MS.

Brain Diseases

Echocardiographic evaluation of changes in cardiac performance induced by hemodialysis.

For the purpose of assessing the cardiovascular effects of hemodialysis (HD), M-mode echocardiography was performed 24 hours before and 2 hours after this procedure in 15 patients with chronic renal failure. The results, which include computer analysis of digitized interventricular septum (IVS) and left ventricular posterior wall (LVPW), show the following statistically significant changes after HD: reduction of end-diastolic and end-systolic internal diameters of the left ventricle (LVID), increase of mean velocity of circumferential fiber shortening, of peak rate of systolic and diastolic LVID variation, of systolic and diastolic LVPW movement, and of IVS movement in systole. These results demonstrate that after HD the left ventricle not only decreases in size but also its performance improves in both contraction and relaxation. These changes did not correlate with the reduction in body weight and arterial pressure following HD; hence HD seems to act on left ventricular function by reducing mainly afterload and, possibly, by modifying some humoral parameters. In conclusion, M-mode echocardiography, especially when utilized in conjunction with the computerized analysis of the recordings, is useful and reliable in monitoring hemodynamic changes occurring during the dialytic session.

Adult

Serial CEA levels in colorectal carcinoma on adjuvant immuno (chemo) therapy.

Serial CEA levels have been studied preoperatively, and one day, 10--15 days, four months, and eight months after surgery in a group of colon cancer patients who started soon after surgery a protocol of adjuvant immuno(chemo)therapy with Levamisole R and BCG R. Results showed a decrease of mean values of plasma CEA levels from preoperatively to four months after surgery, while eight months after surgery a slight increase was noted. Some of the patients in whom disease recurred showed persistent high levels of CEA, while one patient was consistently a false-negative notwithstanding a bone recurrence. While the prognostic value of serial CEA determinations is confirmed, the possibility of restarting (or intensifying) a protocol of adjuvant immunochemotherapy given high CEA levels and a negative clinical picture is discussed.

Adult

Serum complement pattern in essential mixed cryoglobulinaemia.

In twenty-six patients affected by essential cryoglobulinaemia, 188 determinations of serum complement components (SCC) were made. A peculiar pattern was observed which was characterized by: (a) low levels of early components (Clq, Cls and C4), (b) normal levels of C3 and high concentrations of late components (C5, C9) and (c) CH50 values significantly lower than normal. No relationship could be observed between early SCC and C3 levels. Thirty-three crossed immunoelectrophoreses were performed in thirteen patient's blood samples. The C3c peaks were not different from normal. Follow-up data (156 serum samples from twenty-four patients) during a 6-40 month period showed a non-homogeneous SCC behaviour. However, no relationship was found between the complement concentrations and clinical score. These findings suggest that SCC abnormalities are related to a complement hyposynthesis, which could be caused by a reduced C2 production or by a negative feedback effect of active components or their fragments.

Complement C3

Prevalence of anti-HCV antibodies in patients with chronic liver disease and its relationship to HBV and HDV infections.

The prevalence of anti-HCV, anti-HDV and of HBV markers has been investigated in a series of 209 consecutive patients (age 18-74 years) with chronic liver disease. Among 155 HBsAg negative patients (53 chronic hepatitis cases and 102 cirrhosis cases), anti-HCV were found in 69% of the cases. 67% of the 155 patients also carried anti-HBc, with no difference between patients positive or negative for anti-HCV. Among the 54 HBsAg positive patients, 10 (18.5%) also had anti-HCV, 22 (40.7%) were anti-HDV positive and 12 (22.2%) had serum HBV-DNA. One patient had concomitant anti-HDV and anti-HCV and another presented anti-HCV and serum HBV-DNA. 21/54 patients had liver cirrhosis on presentation and among these 17 (81%) were anti-HCV and/or anti-HDV positive. On the whole, 123/209 patients had liver cirrhosis on presentation and in 107 of them HCV infection may have played a role.

Adult

A pathologic correlate of the 'steal' phenomenon in a patient with cerebral arteriovenous malformation.

A patient died after therapeutic bucrylate embolization and resection of a right occipital arteriovenous malformation, which received significant blood supply from the right posterior cerebral artery. At autopsy, there was marked diffuse neuron loss and gliosis in all cell layers of the right hippocampus--pathology which we hypothesize was secondary to a 'steal' of blood from this structure into the malformation. This report represents pathologic evidence for a phenomenon believed to be of major clinical importance in the symptomatology of many AVMs.

Brain

[Enteral nutrition in the elderly].

Elderly is particularly at risk of malnutrition: he is not able to feed himself adequately, it is then important to attain correct intakes using also artificial enteral nutritional techniques (nasogastric tube, gastrostomy, etc.). These techniques may lead to complications (ab ingestis pneumonia, metabolic complications, alvus disorders): the use of artificially nutrition in the elderly must be carefully evaluated. 257 patients (M = 180, F = 77) aged 65 or more, mainly affected by neoplastic diseases (n 195) and by neurological and vascular diseases (n 62). The feeding route were evaluated in this study: 74% by nasogastric tube, 13% by gastrostomy, 11% by jejunostomy. In a group of 55 patients similar concerning clinical and nutritional conditions we evaluated at the beginning of enteral feeding and four months later, caloric/protein intake, body weight and plasmatic albumin. In patients fed by nasogastric tube a mean intake of 1300 +/- 365 Kcal n.p./die, with a protein rate of 58.5 +/- 16.9 g/die was attained; by gastrostomy 1450 +/- 324 Kcal n.p./die and 65.5 +/- 16 g/die; by jejunostomy 1219 +/- 398 Kcal n.p./die and 53.3 +/- 21 g/die. The compliance to enteral nutrition was well in 37% of patients night administration was performed. Clinical complications: nausea and vomiting were observed in 9 patients with nasogastric tube, in 1 patient with gastrostomy and in 3 patients with jejunostomy; diarrhea has been noticed in 6 patients with nasogastric tube and in 1 patient with jejunostomy. Mechanical complications; nasogastric tube (n 189): 35 displacements, 7 breakages, 4 obstructions; pharyngostomy (n 6): 2 displacements and 1 obstruction; gastrostomy (n 33): 3 displacements; jejunostomy (n 29): 2 misplacements.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Role of diet in the treatment of constipation. Review of the literature].

Constipation represents a common social phenomenon today, correlated with the habits of diet and life. Many studies have shown the lack of alimentary fiber as a cause of constipation. In analyzing the different types, the characteristics, the physical and metabolical action of fiber, it has been shown that it is necessary to introduce fiber into the everyday diet to be able to prevent or cure constipation. In addition, it has been seen that there has been a reduction in the consumption of fiber in many nations and some reasons have been investigated.

Constipation