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Biomedical subjects

F Konikoff

Publications and source records attributed to F Konikoff.

At least 37 records · Page 2Linked to original sources

Nodular gastritis and Helicobacter pylori.

Numerous reports have established the association of Helicobacter pylori and peptic ulcer disease in adults. Recently, this association has also been demonstrated in children. We investigated 14 children and adolescents with recurrent abdominal pain. In six patients, endoscopy revealed gastritis and Helicobacter pylori was identified. Giemsa stain was more sensitive than culture or urease testing in identifying the bacteria. In four of the six, a nodular appearance of the antral mucosa was observed. The histological examination suggests lymphoid hyperplasia as the cause of the nodularity. All of the patients became symptomless after combined treatment with amoxicillin and bismuth subsalicylate. We conclude that nodular gastritis is a peculiar type of gastritis in children. It is frequently found in association with Helicobacter pylori infection.

Adolescent↗

Polyamines--potential nucleating factors in bile.

Lithogenicity of human bile is dependent not only on cholesterol saturation, but also on the presence of nucleating and antinucleating factors. Most of the research in this field is directed toward biliary proteins, particularly glycoproteins. In the present study we have shown that spermine, spermidine, cadaverine and putrescine have a nucleating effect in model bile as well as in native human bile. These findings are based on 183 mixing experiments using biles from 10 patients and model biles. The effect seems to be dose dependent at concentrations up to 10 mmol/l. It is not accompanied by a shift in cholesterol distribution between its vesicular and micellar carriers. It is at present uncertain whether these effects are pharmacologic or physiologic. These findings emphasize, however, the potential importance of non-protein compounds in the cholesterol nucleation process in bile.

Bile↗

Biliary micellar cholesterol nucleates via the vesicular pathway.

Biliary cholesterol nucleates primarily from phospholipid vesicles. In this study, we investigated the mode of nucleation of micellar cholesterol. Ten biles (four human and six model) were examined. The vesicular and micellar fractions of each bile were separated by gel chromatography. The whole biles and their isolated carriers were incubated at 37 degrees C until nucleation time. In whole human biles, the proportion of total cholesterol in vesicles rose throughout the incubation (from zero time to nucleation time) from 15.5 +/- 8.6% to 28.0 +/- 12.5%, and in model biles from 46.8 +/- 22.4% to 75.5 +/- 8.2%. The vesicular isolated fraction remained unchanged throughout incubation. In isolated micelles devoid of vesicles at zero time, new vesicles formed during incubation, carrying increasing proportions of cholesterol. At nucleation time, these vesicles contained 11.0% of originally micellar cholesterol in human biles, and 41.2% in model biles. The new vesicles formed in whole bile and in the micellar fraction were chromatographically and chemically similar to the vesicles originally present in bile. These data suggest that micellar cholesterol nucleates via the neoformation of phospholipid vesicles, which seem to be the final common pathway for cholesterol nucleation in bile.

Bile↗

Autoantibodies to histones and their subfractions in chronic liver diseases.

Sera of 78 patients with different chronic liver diseases were examined for the presence of anti-histone activity using an enzyme-linked immunosorbent assay. Eighteen patients had primary biliary cirrhosis (PBC), 20 had chronic active hepatitis, and 40 had cirrhosis. Anti-histone antibodies were detected in 34 patients (43.6%), distributed among all liver disease entities studied. When antibodies of specific isotypes (IgG, IgM, and IgA) were measured, even higher frequencies were noted--50% for IgG and 53.8% for IgA. Antibodies to histone subfractions H1, H2a, H2b, H3, and H4 were also observed in all liver disorders investigated (in 22-32% of patients)--H1 and H3 being the prominent fractions involved. Of the various disease entities examined PBC was the one disclosing the highest frequency of anti-histone antibodies.

Antibodies, Antinuclear↗

Detection of antimitochondrial antibodies: characterization by enzyme immunoassay and immunoblotting.

Mitochondrial antigens were purified from rat liver and characterized by immunoblotting. Sera from 19 well defined patients with primary biliary cirrhosis (PBC) reacted with two mitochondrial polypeptides of 68 Kd and 45 Kd. Antibodies to these antigens were not detected in any of the sera of patients with cirrhosis of the liver, chronic active hepatitis or other autoimmune diseases. The two polypeptides were derived from the soluble fraction of the mitochondrial matrix. An enzyme-linked immunosorbent assay (ELISA) employing these rat liver mitochondrial antigens is described. Positive results were obtained with all except one PBC sera (95%), five out of 47 patients with cirrhosis (11%), one out of 20 patients with chronic active hepatitis (5%), and two out of 19 patients with various autoimmune disorders (11%). The titers detected in PBC were markedly higher than those recorded in patients with other liver and autoimmune diseases. Strong correlation was found between immunoblotting and the ELISA in determining antimitochondrial antibodies. The ELISA presented is easily performed and seems to be a useful diagnostic tool for antimitochondrial antibodies in patients with PBC.

Adolescent↗

Antinuclear autoantibodies in chronic liver diseases.

Circulating autoantibodies are often observed in liver disorders, especially in those thought to have an autoimmune etiology-such as primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH). The pathophysiologic role of these antibodies, however, remains obscure. The present study was performed to evaluate the incidence and diagnostic value of different antinuclear antibodies in chronic liver diseases, and to assess whether the antibodies are a non-specific expression of the hypergammaglobulinemia observed in these disorders. We measured six different antinuclear and closely related antibodies (against ssDNA, dsDNA, Poly (I), Poly (dT), RNA and cardiolipin) and their IgG, IgA and IgM isotypes in the sera of 86 patients with autoimmune, as well as other chronic liver diseases--namely, PBC, CAH, alcoholic (AC) and cryptogenic cirrhosis (CC). Antibodies against all the various nuclear antigens were detected in all diseases studied. The incidence ranged from 4% (anti-cardiolipin-IgG in CC) to 74% (anti-Poly (dT)-IgM in PBC). Although the antibody profiles differed among the various disease entities, they were not distinct enough to be of any clinical diagnostic value. In alcoholic cirrhosis antibody levels correlated with corresponding immunoglobulin isotype levels (notably IgA), suggesting a non-specific expression of hypergammaglobulinemia. In the other liver diseases such a correlation was lacking, favoring the existence of an underlying specific antigenic stimulation, or some other more specific immune dysfunction.

Adult↗

Common lupus anti-DNA antibody idiotypes in chronic liver diseases.

Chronic liver diseases may be associated with the appearance of antinuclear antibodies. To further analyze the relationship between connective tissue and liver diseases the sera of 88 patients with chronic liver disorders were examined for the presence of common lupus anti-DNA idiotypes (16/6-id, 134-id, and 32/15-id), using an enzyme-linked immunosorbent assay. The 16/6-id was found in 58 (65.9%), the 134-id in 43 (48.9%), and the 32/15-id in 13 (14.8%) of the patients' sera. Distinct diagnostic groups displayed different lupus anti-DNA idiotype profiles. Patients with primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH) had mainly the 16/6 idiotype, while in alcoholic (AC) and in cryptogenic cirrhosis (CC) the 16/6-id and 134-id were the main idiotypes recorded. There was considerable correlation among the different anti-DNA idiotypes but not between any of these idiotypes and an unrelated common anti-HBsAg idiotype. The occurrence of the various idiotypes was not found to be correlated with increased serum immunoglobulin levels. It can be concluded that the similarities between chronic liver diseases and connective tissue diseases are extended also to the presence of specific common anti-DNA antibody idiotypes.

Autoantibodies↗

A study of antipolynucleotide antibodies, anti-Klebsiella (K30) antibodies and anti-DNA antibody idiotypes in ankylosing spondylitis.

Recent studies have indicated that both ankylosing spondylitis and the anti-DNA antibodies found in systemic lupus erythematosus may be related to Klebsiella surface antigens. In order to explore these possible relationships further, the sera of 24 patients with ankylosing spondylitis (AS), and 20 controls, have been examined for binding to a wide range of antipolynucleotide antibodies, antibodies binding to the Klebsiella pneumoniae polysaccharide K30 and two DNA antibody idiotypes designated 16/6 and 134. We report that although 21% of the AS patients had IgG ssDNA antibodies it is evident that the aetiopathogenesis of this disease is not through the mechanism of autoantibodies or the common DNA antibody idiotypes tested.

Antibodies, Antinuclear↗

Cholestasis and liver failure with lambda-AL amyloidosis.

Clinically significant liver involvement in systemic amyloidosis, especially with cholestasis, is rare. We report a case of primary amyloidosis with severe intrahepatic cholestasis leading to terminal liver failure. The present case is the first of its kind reported involving Lambda light chains only as the associated paraprotein. Conventional treatment and a therapeutic trial with dimethyl sulphoxide were unsuccessful.

Aged↗

Placental type isoferritins in chronic liver diseases.

Serum ferritin levels in chronic liver diseases were measured by an enzyme-linked immunosorbent assay (ELISA) using two monoclonal antibodies (McAb) against placental ferritin. One of the McAbs (CM-H9) recognizes a specific placental-like isoferritin (PLF) only, while the other McAb (CM-G8) recognizes an isoform (CF) common to human placenta, liver and spleen. The different diseases studied were primary biliary cirrhosis (PBC-14 patients), chronic active hepatitis (CAH-12 patients), alcoholic cirrhosis (AC-18 patients) and cryptogenic cirrhosis (CRY-26 patients). Increased levels of both isoferritine were found in all these liver disorders, with an overall incidence of 80% for CF and 40% for PLF. The mean level of CF was significantly above normal in PBC, AC and CRY and that of PLF in PBC and CRY. Circulating placental-type isoferritins have not been previously described in patients with liver disorders. Our findings indicate that elevation of serum ferritin in liver diseases is caused by different isoferritin components.

Antibodies, Monoclonal↗

Painful muscle cramps. A symptom of liver cirrhosis?

We found an 88% incidence of painful muscle cramps in 33 patients with cirrhosis, as compared to 21% in a matched population without liver disease. The cramps were characterized by severe pain, occurred in calf muscles several times a week (mainly at rest or during sleep), and lasted for a few minutes. No definite etiological factor could be found and the underlying pathophysiology remains obscure, as in most other types of muscle cramps. However, the strikingly high incidence and uniformity of the phenomenon may justify the inclusion of painful muscle cramps among the recognized symptoms of cirrhosis.

Female↗

Cloxacillin-induced cholestatic jaundice.

A case of cholestatic jaundice after cloxacillin treatment is presented. Hepatotoxicity due to the drug was confirmed by inadvertent rechallenge and strongly positive tests for macrophage migration inhibitory factor and mast cell degranulation. The recognition of cholestatic hepatotoxicity due to oxacillin derivatives should help to avoid unnecessary invasive procedures in the evaluation of this reversible condition.

Aged↗

Effects of salt loading during exercise in a hot dry climate.

Strenuous work or sports activities in a hot environment can cause significant fluid and salt losses due to excessive sweating. Fluid replacement is commonly accepted to be beneficial, but controversy surrounds the necessity of adding salt to the dietary intake in hot climates. Five healthy young men participated in a self-controlled experiment designed to investigate the effects of salt loading on acclimatized people exercising under controlled laboratory conditions. The additional salt ingestion was found to cause an increase in body weight, rectal temperature, heart rate, urinary sodium and potassium concentrations and in the total amounts of sodium and chloride excreted in urine during the exercise. Furthermore, it decreased plasma aldosterone level and sweat chloride excretion, but did not affect fluid intake, urine output, sweat rate, skin temperature, excretion of sodium and potassium in sweat or urinary potassium content and chloride concentration. Neither did the additional salt intake affect plasma electrolyte levels, renin activity or acid base balance. It is concluded that acclimatized people living in a hot dry climate need no supplementary salt to their daily dietary intake while engaging in physical exercise or sports activities up to two hours a day. Salt loading has no beneficial effects in these conditions and may even be hazardous.

Acclimatization↗