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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 271 records · Page 15Linked to original sources

Changes in the connective tissue proteins, glycosaminoglycans and calcium in the arteries of the cynomolgus monkey during atherosclerotic induction and regression.

The chemical composition of the aorta, carotid, coronary and cerebral arteries of the cynomolgus monkey was determined during the induction and 'regression' of atherosclerosis. The feeding of a 2% cholesterol and 10% butter diet for 6 months resulted in extensive and severe atherosclerosis involving the aorta, carotid and coronary arteries. The involvement of these vessels was reflected by increases in arterial weight and chemical content of cholesterol, collagen, elastin, glycosaminoglycans (GAGs) and calcium. The cerebral arteries, which showed no atherosclerotic involvement, likewise showed no significant changes in weight and composition. During the 12-month regression period marked changes in the chemical composition of the involved arteries occurred and these included further increases in the collagen, GAG and calcium content of the vessels and decreases in the free and esterified cholesterol content. These changes were consistent with the gross and microscopic findings which revealed that during regression the pre-established lesions had not decreased in size but had become more fibrotic and calcified while the number of foam cells and amount of lipid contained in the lesion had decreased. During induction and regression, much of the cholesterol contained in the involved vessels appeared to be present in a crystalline form as indicated by the appearance of cholesterol clefts in the lesions. Aortic collagen was not altered with respect to amino acid composition and behavior in acrylamide gels throughout the study. However, elastin prepared by hot alkali treatment from diseased vessels, showed minor changes in amino acids during induction and marked changes during regression presumably due to the binding of glycoproteins to the elastin. The GAG composition of the involved arteries did not change during induction, whereas during regression the percent dermatan sulfate increased while the percent of heparan sulfate decreased. The over-all findings are consistent with the concept that the interaction of the connective tissue proteins with the GAGs, lipoproteins and calcium of the artery plays an important role in the development and regression of advanced atherosclerotic disease.

Animals↗

Decrease in suppressor/cytotoxic T-cells with histamine receptors in patients with chronic active hepatitis.

A fluorescence assay was employed to measure the levels of circulating suppressor/cytotoxic T cells with membrane receptors for histamine (H+T cells) in 33 patients with chronic active hepatitis, in seven patients with metabolic and vascular liver disorders and in 25 healthy individuals. The H+T cells were decreased in patients with CAH (4.6 +/- 2.2 cells/mm3 vs 16 +/- 3.9 cells/mm3; p less than 0.001), but were normal in patients with metabolic or vascular liver diseases (17.6 +/- 6 cells/mm3 vs 16 +/- 3.9 cells/mm3; NS). Patients with HBsAg-negative CAH had fewer circulating H+T cells than those with HBsAg-positive CAH (p less than 0.05). The same was true for patients with cirrhosis as compared to those without. The lymphocyte alterations were independent of the nature and course of CAH, but correlated inversely with the serum levels of gammaglobulins and with the histological features of hepatic inflammation (p less than 0.05). Like other sets of lymphocytes, the H+T cells in CAH may have locally either immunomodulatory or cytotoxic effects. In analogy with other immune disorders (histiocytosis X, atopic dermatitis), one might speculate that the alterations in H+T cells in CAH represent derangement of the immunoregulatory cell network. The absence of systemic features of autoimmunity in viral CAH correlates with the demonstration that H + T cells exert their immunoregulatory effects at the sites of inflammation where histamine is being released.

Adolescent↗

[Altered immunoregulation in chronic viral hepatitis. Deficiency of T-lymphocytes with membrane receptors for histamine].

To further characterize the defect of immunoregulation in chronic active hepatitis (CAH), we measured circulating T cells with membrane receptors for histamine (H + TLy), cells endowed with cytotoxic and suppressor functions, in a group of patients with viral CAH, in patients with non-immune liver disorders and in healthy individuals. Patients with CAH showed significantly lower mean numbers and percentage of H + TLy (p less than 0,001) than controls, while patients with non-immune liver disorders had H + TLy values which did not differ significantly from those found in healthy individuals. The lymphocyte alterations in CAH patients were independent of serum HBsAg, cirrhosis or steroid therapy, but correlated inversely with an in vivo index of plasma cell activity, i.e., serum gammaglobulin levels, and with the histological parameter of hepatic inflammation, i.e. portal and periportal mononuclear infiltration. The normal values of H + TLy in patients with non-immune liver diseases suggest that in CAH the decrease in circulating H + TLy is not secondary to the liver damage. The alteration of immunoregulation associated with CAH may have pathogenetic implications, although it is unlikely to represent the sole mechanism for the perpetuation and worsening of the disease process.

Adult↗

Histological maturation of the neocortex in phenylketonuric rats.

The histological maturation of pyramidal cells from the deeper layer of the neocortex was studied in phenylketonuric rats. The main alterations consist of a decrease in the number of span and dendritic basilar processes of large pyramidal cells, and changes in the structural organization of the cerebral cortex. It is postulated that high levels of phenylalanine induced immediately after birth disturb profoundly the process of neuronal maturation in the neocortex of the rat brain, probably with long-term effects.

Animals↗

Serum marker of type III procollagen in patients with idiopathic hemochromatosis and its relationship to hepatic fibrosis.

A radioimmunoassay for serum procollagen III aminopeptide (sPIIIP) was proposed recently for monitoring hepatic fibroplasia in patients with various inflammatory hepatic lesions. To determine whether sPIIIP also can detect fibroplasia in noninflammatory liver disorders, we measured this index in 16 patients with idiopathic hemochromatosis (IHC) at various stages of the disease and iron overload. Interestingly, we found normal levels of sPIIIP in 12 out of 16 patients examined (75%), despite clear histologic features of fibrosis or cirrhosis. The levels of sPIIIP exhibited no relationship to any of the clinical, laboratory, or histologic parameters of the disease. Thus, unlike other types of cirrhosis, in which sPIIIP is increased, the liver disease in IHC may be a fibrotic process unrelated to type III collagen stimulation. Accordingly, the determination of sPIIIP in these patients is of no value for monitoring the fibrosis associated with the liver disease.

Adult↗

Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment.

To assess the characteristics of chronic hepatitis in hepatitis B surface antigen (HBsAg) carriers with intrahepatic delta antigen, the hepatic histologic findings of 137 patients were reviewed; 101 patients were followed for 2 to 6 years. The predominant liver disease was chronic active hepatitis in 93 patients or cirrhosis in 32; minor forms of chronic persistent or lobular hepatitis were seen in 12 patients. Eight of the 26 patients with an initial diagnosis of cirrhosis died during the follow-up period. Cirrhosis developed in 31 of 75 patients (41%) without nodular regeneration seen in the first biopsy specimen; 5 of these patients died. Treatment with prednisone or azathioprine did not induce histologic amelioration of delta hepatitis or prevent cirrhosis. Chronic HBsAg hepatitis with intrahepatic expression of the delta antigen is an active, progressive disease unresponsive to conventional immunosuppressive treatment.

Adolescent↗

In situ characterization by monoclonal antibodies of the mononuclear cell infiltrate in chronic active hepatitis.

To characterize the inflammatory infiltrate of chronic active hepatitis we have examined 26 liver biopsy specimens [16 hepatitis B surface antigen-negative and 10 hepatitis B surface antigen-positive] with monoclonal antibodies and antiimmunoglobulins that react against the following mononuclear cell populations: T cells, T4 cells, T8 cells, monocytes-macrophages, Ia-positive cells, surface Ig-bearing cells, natural killer/killer cells. A biotin-avidin-fluorescein technique was used and the number of positive cells was counted in a portal tract that was more severely involved. The T cells predominate in all the specimens. The T4:T8 cell ratio and the number of T and T4 cells in the hepatitis B surface antigen-negative patients are higher than in the hepatitis B surface antigen-positive patients. While natural killer/killer cells, surface Ig-bearing cells, and macrophages are always rare, Ia-positive cells are numerous and the double-staining technique demonstrates a fair number of cells displaying both T-cell and Ia markers. These findings, while not supporting a major role of killer cells in chronic active hepatitis, suggest a different alteration of T-cell subsets in hepatitis B surface antigen-positive and -negative chronic active hepatitis.

Adult↗

Long-term delta superinfection in hepatitis B surface antigen carriers and its relationship to the course of chronic hepatitis.

To assess the prevalence and clinical significance of delta-infection in chronic hepatitis B surface antigen carriers, we examined 326 liver biopsies from 192 retrospectively selected carriers by immunofluorescence. Delta antigen was detected in 102 specimens from 50 carriers (26.2%) with peak prevalence in patients with active cirrhosis (51.5%) and generally in close association with progressive liver disease (94%). The antigen was located in the nuclei of 2%-50% of the hepatocytes, without any disease-specific pattern of fluorescence. Patients with intrahepatic delta-antigen, however, had more severe liver disease than those without it. Histologic follow-up of 101 cases showed that the rates of worsening of the liver disease were similar in delta-antigen-positive and in delta-antigen-negative patients. It is concluded that delta-superinfection does play a role in worsening the histologic picture of hepatitis B surface antigen-positive chronic active hepatitis, possibly by liver injury induced acutely at the moment of infection.

Adolescent↗

Urinary tract infections in the aged: improvement with thymostimulin.

30 aged patients, with chronic urinary tract infections, were treated with a thymus extract (thymostimulin, TP-1 Serono), in combination with antibiotic therapy, according to the antibiogram data, or with antibiotic therapy alone. When thymus extracts were added to the treatment, an improvement of the clinical course of the disease was observed and the severity and duration of the subjective symptoms such as strangury, dysuria, and pollakiuria, were reduced. The two groups of patients presented no modifications of the febrile patterns, nor persistence in or recovery from infection after 30 days of treatment, but especially after 90 days, the frequency of reinfections or the persistence of infections were markedly reduced. During treatment with thymostimulin, there was an evident increase in the cellular immunity tests (T-lymphocytes, rosettes, PHA) as compared with the immunodepression found before treatment.

Aged↗

Cross-reactions between tumor cells and allogeneic normal tissues. Inhibition of a syngeneic lymphoma outgrowth in H-2 and non-H-2 alloimmune BALB/c mice.

To test whether alloimmunization with H-2 or/and non-H-2 different normal tissues may increase the immunity to syngeneic tumors, groups of BALB/c (H-2d) mice were immunized with a series of allogeneic lymphoid cells and then challenged i.p. with syngeneic lymphoma cells. The outgrowth of otherwise lethal doses of the Moloney virus-induced lymphoma YC8 and of its clones was inhibited in BALB/c mice immune to DBA/2 (H-2d), C3Hf (H-2k), C3H.SW (H-2b), C3H.OH (H-2o2) and to B10 background tissues but not in mice immunized to A/He, BALB.K (H-2k) or BALB.B (H-2b) normal tissues. Anti-YC8 effect was also induced by immunizing BALB/c recipients with a pool of five different allogeneic cell lines which included C3Hf, C57BL/6J (H-2b), N:NIH (H-2q), B10.M (H-2f), and DBA/2 lymphoid cells. No growth inhibition of other BALB/c lymphomas induced by Moloney virus (LSTRA), X-rays (RL male I) or urethane (UR-1) was evident in alloimmune mice. In vivo transfer of growth inhibition of YC8 was obtained with BALB/c anti-B10.D2 peritoneal exudate cells in a Winn assay. The ability of these alloimmune lymphoid cells to delay significantly the survival time of BALB/c mice injected with the mixture of immune cell and YC8 cells was abrogated by anti-Thy 1.2 plus C' treatment. In addition, nu/nu BALB/c mice were unable to develop resistance to YC8 outgrowth after alloimmunization. The results of this study show that: (1) syngeneic growth of a lymphoma can be prevented by alloimmunization with normal cells; (2) this cross-reaction involved non-H-2 antigens; (3) the phenomenon appeared to be mediated by T cells.

Animals↗