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Biomedical subjects

M Lenzi

Publications and source records attributed to M Lenzi.

At least 19 recordsLinked to original sources
PubMed1992

Demonstration of peptide-specific and cross-reactive epitopes in proteins reacting with antimitochondrial antibodies of primary biliary cirrhosis.

Recently the main targets of antimitochondrial antibodies (AMA) of primary biliary cirrhosis have been identified as parts of three related mitochondrial multienzyme complexes, namely pyruvate dehydrogenase (PDH), branched chain alpha-ketoacid dehydrogenase (BKDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH). Usually AMA-positive PBC serum samples show reactivity to more than one of these, raising the question whether they are exclusively different antibodies or are, at least in part, the result of cross-reactive specificities. With Western immunoblotting, four antigens with molecular masses of 74, 52, 51 and 43 kDa, are recognized by PBC sera. In this study, using affinity purified antibodies from mitochondrial proteins immobilized on nitrocellulose blots, we demonstrate the presence of peptide-specific and cross-reactive epitopes in some targets. In particular, at least three different epitopes present in the 74-kDa protein (presumed to by PDH-E2) are also present in the 51-kDa protein (probably PDH-X), and two in the 52-kDa peptide (possibly BCKDH-E2). Moreover, the 43-kDa mitochondrial protein (the identity of which is more problematic) has three epitopes. One of these is also present in the 74-, 52- and 51-kDa proteins, a second in the 74- and 51-kDa, and a third seems to be peptide-specific. These results show that different sera with the same immunoblotting pattern of reactivity can have antibodies with different antigenic specificities and, conversely, that the same specificity can be responsible for more than one band.

Adult↗
PubMed1992

Serum autoantibodies and the diagnosis of type-1 autoimmune hepatitis in Italy: a reappraisal at the light of hepatitis C virus infection.

Antinuclear antibodies with the homogeneous pattern (ANA-H) and smooth muscle antibodies with antiactin specificity (SMA-AA) are regarded as the serum markers of type-1 autoimmune chronic hepatitis. Their diagnostic relevance, however, has been questioned recently after the detection of signs of hepatitis C virus infection in autoimmune chronic hepatitis patients. To further evaluate this point, antihepatitis C virus antibodies were sought by two second generation assays (ELISA 2 and RIBA 2) in 100 Italian patients with chronic liver disease of unknown aetiology, including 46 with (autoimmune chronic hepatitis) and 54 without the above antibodies (cryptogenic). By ELISA 2, antihepatitis C virus, although significantly prevalent in cryptogenic (83%), were found also in a substantial proportion of autoimmune chronic hepatitis patients (46%) (p < 0.0001), their occurrence was confirmed by RIBA 2 in almost all cases (96% and 86%, respectively). Autoimmune patients with either ANA-H or SMA-AA exhibited similar antihepatitis C virus prevalences (59% and 52%, respectively); by contrast, the eight cases positive for both the autoantibodies were consistently antihepatitis C virus negative. These findings confirm that in countries with high hepatitis C virus circulation (like Italy) an overlap between autoimmune chronic hepatitis and hepatitis C virus infection, reflected by 'true' antihepatitis C virus antibodies, does occur. The detection of ANA-H or SMA-AA, in fact, identifies chronic liver disease patients with a relatively low prevalence of antihepatitis C virus, but does not exclude hepatitis C virus infection. Positive findings for both ANA-H and SMA-AA, however, is an appropriate marker for hepatitis C virus free 'primary' autoimmune chronic hepatitis.

Actins↗
PubMed1991

Antibodies to hepatitis C virus in autoimmune liver disease: evidence for geographical heterogeneity.

To resolve conflicting reports about the occurrence of antibodies against hepatitis C virus (HCV) in patients with autoimmune chronic active hepatitis (AI-CAH), sera from UK and Italian patients were tested with the original anti-HCV assay (Ortho) and a novel anti-HCV assay (UBI) based entirely on synthetic HCV peptides. 28 (60%) of 47 Italian patients with type-1 AI-CAH were anti-HCV-positive by Ortho ELISA, 25 of whom were also strongly positive by the UBI assay. 15 (60%) of 25 UK patients with type-1 AI-CAH were HCV-positive by Ortho ELISA but only 2 were positive by the UBI assay. Similarly, 29 (88%) of 33 Italian patients with type-2 AI-CAH, but 0 of 10 UK patients, were very strongly anti-HCV-positive with the UBI assay. Italian patients with AI-CAH appear to have a high frequency of genuine exposure to HCV, whereas seropositivity by the Ortho HCV ELISA in UK patients is likely to represent a false-positive result. These findings indicate important geographical and/or genetic influences in autoimmune liver disease among different populations.

Adult↗
PubMed1991

Hepatitis C viraemia in adults with type 2 autoimmune hepatitis.

Sera from 14 patients with type 2 autoimmune hepatitis (anti-LKM1 positive) were investigated for evidence of hepatitis C virus (HCV) infection. Antibodies to HCV were detected in 13 patients by both commercial and "in-house" ELISAs and also by a second generation recombinant immunoblot assay. Nine of the 13 (69%) anti-HCV positive patients were shown to be viraemic by a polymerase chain reaction-based assay for serum HCV RNA. Neither anti-HCV nor serum HCV RNA were detected in any of 6 controls with primary biliary cirrhosis or in 39 healthy blood donors. These findings strongly suggest a role for HCV in the pathogenesis of type 2 autoimmune hepatitis.

Adolescent↗
PubMed1991

Anti-nuclear antibodies of primary biliary cirrhosis recognize 78-92-kD and 96-100-kD proteins of nuclear bodies.

The specificities of anti-nuclear antibodies (ANA) reacting with multiple nuclear dots (MND-ANA) present in about 15% primary biliary cirrhosis sera were studied by Western blot analysis with nuclear fractions from a human cell line. Reactivity with two broad bands of 78-92 kD and 96-100 kD of the insoluble fraction was present exclusively in MND-ANA-positive sera. Antibodies eluted from these proteins specifically retained the immunofluorescence reactivity of MND-ANA. Immunomorphological analysis by a pre-embedding technique revealed that the antibody specifically binds to nuclear regions resembling in size and number nuclear bodies. Since these structures are absent in immature rate endometrial cell and can be induced by diethylstilbestrol, we tested MND-ANA by immunofluorescence on cryostat sections of uteri from hormone-treated and untreated immature rats. A strong reaction of nuclear dots was observed predominantly in endometrial cells of hormone treated rats. We thus conclude that MND-ANA present in primary biliary cirrhosis sera are directed against 78-92-kD and 96-100-kD nuclear proteins located in nuclear bodies.

Animals↗
PubMed1990

Anti-actin antibodies: a new test for an old problem.

Smooth muscle antibodies with anti-actin specificity are commonly regarded as markers of autoimmune liver disease. However, there are interpretational problems because different techniques have been used for their identification and therefore the results are difficult to compare. The present paper reports the results of a new method for the identification of anti-actin antibodies (indirect immunofluorescence on cryostat sections of liver from rats chronically injected with phalloidin). The results have been compared with those obtained by four other techniques: demonstration by immunofluorescence of kidney peritubular reactivity (SMAT), of anti-microfilament antibodies (on HEp-2 cells and vinblastine-treated peripheral blood mononuclear cells) and counterimmunoelectrophoresis with purified muscle actin as antigen. The new method proved to be the most sensitive and specific. Furthermore, its reproducibility was found to be high, the interpretation easy and the cost low. The clinical significance of anti-actin antibodies in patients with chronic liver disease is also discussed.

Actins↗
PubMed1990

Type 2 autoimmune hepatitis and hepatitis C virus infection.

The prevalence of serum antibodies to hepatitis C virus (HCV) was assessed by an enzyme-linked immunosorbent assay in 46 patients seropositive for liver-kidney microsomal antibody (anti-LKM1), the marker of autoimmune hepatitis type 2. 43 had chronic hepatitis (with histological confirmation in 34) and 3 were seropositive for anti-LKM1 without clinical or biochemical evidence of liver damage. The overall prevalence of anti-HCV was 78.2% or 86.1% in patients with chronic hepatitis--a similar prevalence to that reported in patients with chronic non A, non B posttransfusion hepatitis. HCV infection may lead to altered expression of the hepatocellullar LKM1 target antigen, with loss of tolerance and appearance of anti-LKM1 in serum.

Animals↗
PubMed1990

Nifedipine interactions in hypertensive patients.

Nifedipine interactions in hypertensive patients have been evaluated, taking into account both the possibility that the inhibition of prostaglandin (PG) synthesis induced by non-steroidal antiinflammatory drugs (NSAIDs) can reduce the antihypertensive effect of nifedipine and the interactions of nifedipine with other antihypertensive drugs. While the inhibition of systemic and renal PG synthesis induced by indomethacin reduces the hypertensive effect of many drugs, it does not change the antihypertensive effect of nifedipine. The combination of two antihypertensive drugs with different mechanisms of action is often needed in the treatment of hypertensives, since it is well known that monotherapy is able to normalize BP in no more than 50% of mild to moderate hypertensives, and the rationale to combine two antihypertensive agents is based on the knowledge that their combination exerts an additive antihypertensive effect when compared with single-drug treatment. While it is well established that nifedipine can be usefully combined with beta blockers, ACE inhibitors, and clonidine, it is still controversial whether the combination of nifedipine with a thiazide diuretic exerts an additional antihypertensive effect. We have previously shown that the acute hypotensive effect of nifedipine in patients with chronic renal failure is greater during sodium repletion than during sodium depletion, and that chlorthalidone, compared with placebo, does not increase the hypotensive effect of nifedipine in essential hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

[Treatment of septic complications in diverticular disease of the colon].

Eight years' experience in the treatment of the septic complications of diverticular disease of the colon is examined and 44 cases treated in the period 1980-1988 are considered. The Hartman procedure gave good results in the majority of cases; other procedures such as drainage with colostomy, or anastomosis resection during a single intervention are reserved for particular cases. In addition, on examining the case histories and the current literature it seems that it is correct to treat DD (diverticular disease) surgically whenever the typical manifestations of the overt disease appear; waiting often represents nothing more than a postponement of the surgical treatment until an emergency arises.

Aged↗
PubMed1989

Naloxone does not antagonize the antihypertensive effect of chronic captopril therapy in hypertensive patients.

It has been reported that naloxone, an opiate receptor antagonist, blunts the hypotensive effect of captopril in normotensives. However, our previous data did not show any interaction between captopril given acutely and naloxone (0.1 mg/kg) in hypertensives. To test whether a greater naloxone dose could interfere with the hemodynamic effect of chronically administered captopril, 12 male hypertensives were studied: Six of them had been under captopril treatment (50 mg tid) for at least 1 month, whereas the others had been drug free for the same time. Both groups randomly received a saline or naloxone (0.2 mg/kg) infusion for 1 hour, and blood pressure, heart rate, PRA, plasma aldosterone, adrenaline, and noradrenaline were measured at regular intervals before, during, and after naloxone infusion. In drug-free hypertensives, naloxone tended to reduce blood pressure slightly and did not modify heart rate, PRA, plasma aldosterone, adrenaline, or noradrenaline. In captopril-treated hypertensives, naloxone did not blunt the hypotensive effect of captopril, but rather enhanced it, without changing the heart rate, adrenaline, and noradrenaline. Moreover, naloxone increased the renin-stimulating action and did not modify the aldosterone-inhibiting effect of captopril. Our results show that the hemodynamic action of captopril given chronically is not influenced by opioid receptor blockade and therefore that the antihypertensive effect of this drug seems to be unrelated to the activation of the opioidergic system.

Adult↗
PubMed1989

Acute hemodynamic (systemic and renal) and humoral effects of three increasing doses of iloprost in essential hypertensives.

To evaluate the acute hemodynamic, both systemic and renal, and humoral effect of three increasing doses of Iloprost, a prostacyclin analogue, eight uncomplicated untreated hospitalized patients with mild to moderate essential hypertension, while on a constant sodium and potassium intake, received, after oral hydration, three doses of Iloprost (1,2 or 4 ng/kg/body weight for 45 min) in a single-blind randomized sequence. Each dose was preceded by placebo (saline infusion for 45 min) with a 48 h interval between each study. Iloprost significantly (P less than .05) reduced blood pressure, and increased heart rate, filtered sodium, urinary sodium excretion, fractional sodium excretion, noradrenaline, adrenaline, and plasma renin activity (PRA). The blood pressure lowering effect as well as the heart rate, renal plasma flow and noradrenaline increases were significantly greater on the 4 ng dose. Glomerular filtration rate and adrenaline showed a dose-dependent increase; urinary sodium excretion and fractional sodium excretion were similarly increased by the three doses. No correlation was found between urinary sodium excretion and either glomerular filtration rate or renal plasma flow. The data obtained indicate that Iloprost causes reduction of blood pressure with a reflex activation in the sympathetic nervous system and stimulation of renin secretion, renal vasodilation mainly at the level of the afferent arteriole, and natriuresis. This latter effect is probably due to a direct inhibition of tubular reabsorption, which, at variance with the other effects, is dose-independent.

Adult↗
PubMed1989

Immune dysfunction in primary biliary cirrhosis. II. Increased production of prostaglandin E.

In a previous study we observed that after in vitro treatment with indomethacin, lymphocyte response to phytohaemagglutinin (PHA) in primary biliary cirrhosis (PBC) patients was higher than that of controls. We know that indomethacin also inhibits prostanoid production, and thus in the present work we directly measured prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production by mononuclear cells and monocytes from 12 PBC patients, 11 control subjects, and three control disease patients (alcoholic cirrhosis, AC). PHA-stimulated enriched monocytes from PBC patients produced approximately threefold more PGE2 (after 48 h of culture) than did normal and AC monocytes (P less than 0.05). TXB2 production was similar in all groups studied. We also made cultures in which PBC-purified lymphocytes proliferated better than PBC mononuclear cells (i.e. lymphocytes plus monocytes). Thus, a monocyte population producing PGE2 could be responsible, at least in part, for the hyporesponsiveness to PHA observed in PBC patients.

Humans↗