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Biomedical subjects

R Uibo

Publications and source records attributed to R Uibo.

At least 55 records · Page 3Linked to original sources
PubMed1995

Association of Helicobacter pylori gastric infection with the suppressed Thomsen-Friedenreich antigen natural humoral response.

BACKGROUND: A low natural humoral immune response to Thomsen-Friedenreich antigen (TFA) is a general phenomenon in patients with cancer, including gastric cancer, and in some premalignant conditions. It has been also shown that Helicobacter pylori infection is associated with increased risk of gastric cancer. The possible link between the TFA immune response and H. pylori infection was investigated. METHODS: Enzyme-linked immunosorbent assay with H. pylori cell surface glycine extract as antigen and microhemagglutination of neuraminidase-treated blood group O donor erythrocytes were used for evaluation of IgG H. pylori antibody and TFA agglutinin levels in sera from patients with gastric cancer (n = 39) or ulcer of the stomach (n = 36) and controls (n = 49). RESULTS: The tendency to an inverse relationship between the two events was found in all groups studied, including cancer. H. pylori-seronegative persons had higher TFA natural antibody titer than the related H. pylori-seropositive groups. When log2 of TFA antibody titer > 4 for strong TFA responders and H. pylori relative antibody activity > 25 for H. pylori-seropositive persons were chosen as cut-off limits, the association was statistically significant (p < 0.02). TFA antibody level was decreased in cancer patients as compared with controls (p < 0.002). No relation to age, stage of the disease, or tumor morphology was noted. CONCLUSION: The data suggest that the TFA natural immune response, which is known to participate in tumor-host relationships, is also involved in H. pylori-host interactions, probably as a natural factor of resistance against H. pylori infection.

Antibodies↗
PubMed1995

Primary biliary cirrhosis in Estonia. With special reference to incidence, prevalence, clinical features, and outcome.

BACKGROUND: Primary biliary cirrhosis (PBC) is a liver disease of unknown etiology, whose occurrence varies greatly between different regions. For a long time there have been no published data about the incidence and prevalence of PBC from Eastern Europe countries. METHODS: The incidence and prevalence of PBC have been investigated in the Estonian population during the period 1973-92. Two sources of information were used: an information circular/questionnaire was sent to all district hospitals and gastroenterologists, and the case histories of all patients with a positive antimitochondrial antibody titer of 1:40 or more were reexamined. RESULTS: During this period 69 cases of PBC were diagnosed. The male to female ratio was 1:22; 13% of the patients were asymptomatic. The mean annual incidence was 2.27 per million, and on 31 December 1992 the point prevalence was 26.9 per million. There were differences in prevalence among the various districts of Estonia. Associated autoimmune conditions were reported in 32% of the patients. Mean survival from the time of diagnosis was 52.5 months. CONCLUSIONS: The incidence of PBC in Estonia is at the lower end of the range reported in the world literature. This has probably partly been caused by a low percentage of asymptomatic and male patients.

Adult↗
PubMed1994

Characterization of adrenal autoantigens recognized by sera from patients with autoimmune polyglandular syndrome (APS) type I.

Steroidogenic enzymes P450scc, P450c17 and P450c21 have recently been shown to be the main autoantigens recognized by sera from patients with autoimmune polyglandular syndrome (APS type I) with or without Addison's disease. We have studied the interrelationships of autoantigens revealed with APS type I sera in the adrenal and in placenta by immunodiffusion and immunoblotting, and correlated the findings to reactivities towards the above steroidogenic enzymes. We studied 50 patients with APS type I, 36 of whom also had Addison's disease, three patients with isolated (adult type) Addison's disease, seven healthy relatives of the patients with APS type I, 18 patients with insulin-dependent diabetes mellitus, 17 patients with autoimmune liver disease and 26 healthy controls. Immunodiffusion revealed two precipitating autoantigens in adrenal gland, and one of these was also found in placenta. In immunoblotting, five major adrenal antigens with molecular sizes of 55 kDa, 48 kDa, 43 kDa, 39 kDa and 19 kDa were seen. Reactivity to the 55 kDa, 39 kDa or 19 kDa represents the occurrence of antibodies to P450c17 or to its components as revealed by comparative studies with mouse antibodies to recombinant P450c17. These three bands in immunoblot as well as precipitating antibodies were observed exclusively in APS type I patients who had or developed Addison's disease. The 48 kDa antigen was found also in placenta and is probably P450scc, judged by the high correlation of P450scc antibodies with immunodiffusion and immunoblotting results using placental homogenate. There was no association between reactivity to the 43 kDa band and other immune parameters studied. The results thus indicate that P450scc and P450c17 enzymes are the precipitating adrenal autoantigens recognized by sera from APS type I patients. However, according to immunoblot results there could be some yet unidentified adrenal autoantigens to which APS type I patients could develop antibodies.

Addison Disease↗
PubMed1994

Enzyme-linked immunosorbent assays for the determination of IgG, IgA, and IgM autoantibodies to pyruvate dehydrogenase in primary biliary cirrhosis.

Autoantibodies to the recently described mitochondrial autoantigen, pyruvate dehydrogenase, have been shown to be specific for primary biliary cirrhosis. In the present study we describe enzyme-linked immunosorbent assays to detect antibodies of IgG, IgA, and IgM classes reactive with pyruvate dehydrogenase. These assays showed high sensitivity (95%) and specificity (100%) for primary biliary cirrhosis when evaluated in 28 patients with primary biliary cirrhosis, 59 disease controls, and 214 healthy persons. Quantitation of these autoantibodies by calculating the areas under the sera titration curves of 10 primary biliary cirrhosis patients indicated that an increase in IgA antibodies to pyruvate dehydrogenase is related to more rapid disease progression.

Autoantibodies↗
PubMed1994

Autoantibodies to cytochrome P450 enzymes P450scc, P450c17, and P450c21 in autoimmune polyglandular disease types I and II and in isolated Addison's disease.

Patients with idiopathic Addison's disease have autoantibodies reacting with adrenal cortex. If Addison's disease is associated with other endocrine immune diseases like autoimmune polyglandular diseases (APD) type I and type II, antibodies may recognize all steroid-producing cells. We showed previously that one antigen recognized by APD-I sera is the cytochrome P450c17 hydroxylase. We have now looked for antibodies to P450c17 and to two other key enzymes in the steroid biosynthetic pathway, the P450scc and P450c21, in a series of patients with isolated Addison's disease (8 patients) or with APD-I or APD-II (50 and 9 patients, respectively). The result of antienzyme antibodies were further correlated with the immunofluorescence pattern against adrenal gland, testis, ovary, and placenta, and with the clinical findings presented. In APD-I patients with Addison's disease and in APD-II patients, antibodies to at least one of the P450 enzymes were frequently found (positive findings in 81% and 78%, respectively). Such antibodies were less frequent in APD-I patients without Addison's disease (21%) and in the isolated Addison cases (25%). In APD-I, antibodies recognized as frequently P450c17 and P450scc, specific for all steroid-producing cells as the adrenal specific enzyme P450c21. In contrast, patients with APD-II or with the isolated Addison's disease reacted almost exclusively with P450c21. Immunofluorescence studies showed good correlation with the known fact that the zona glomerulosa of the adrenal cortex is devoid of the P450c17, that the Leydig cells of the testis and the theca interna cells of the ovary express P450c17 and P450scc, and that the placental trophoblasts express only P450scc. The presence of antibodies to P450scc or to at least one of the tested P450 enzymes correlated significantly to gonadal failure in the females but not in the males.

Addison Disease↗
PubMed1993

Serum IgA anti-gliadin antibodies in an adult population sample. High prevalence without celiac disease.

IgA-class anti-gliadin antibodies (AGA) and IgA-, IgG-, IgM-class anti-reticulin antibodies (ARA) were determined in 1461 persons, representing 84% of a population from the village of Karksi-Nuia. AGA were detected by enzyme-linked immunosorbent assay (ELISA) and ARA by indirect immunofluorescence. Fifty-two (3.5%) persons had IgA-class AGA, of whom 48 and an additional three of four persons with diarrhea were biopsied. All biopsies showed normal small intestinal mucosal architecture. All 1461 persons were negative for ARA. Our results demonstrate that AGA are frequently detected in an adult Estonian population and positivity increases with age in persons with normal small intestinal mucosa. Positivity for AGA does not predict silent undetected celiac disease but rather represents a normal response to dietary antigens in the elderly. Inability to detect ARA suggests that celiac disease does not exist in this population. As none of the AGA-positive but ARA-negative biopsied persons had celiac disease, ARA might be a more specific serologic marker for celiac disease than AGA.

Adult↗
PubMed1992

Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alpha-hydroxylase.

Idiopathic Addison's disease is characterised by a progressive failure in the synthesis of all classes of steroid hormones and by an immune response against the steroid-producing cells of the adrenal cortex; the nature of the adrenal autoantigens is not known. We have used molecular cloning and sequencing to identify the target antigens. We screened a human fetal adrenal cDNA expression library in lambda gt11 vector with serum samples from patients with Addison's disease as part of the type 1 polyendocrine autoimmunity syndrome. Samples from 3 patients, which had precipitating antibodies against two adrenal proteins detected by immunodiffusion and against five adrenal proteins of molecular mass 55, 48, 43, 39, and 19 kDa as judged by immunoblotting, were used to identify 60 immunoreactive clones. 39 of these were subcloned, inserted into the M13mp10 vector, and sequenced by the dideoxy method or identified by Southern and dot-blot hybridisation. All but 1 of the inserts showed more than 98.8% homology with the published sequence of steroid 17 alpha-hydroxylase. This protein was expressed by insertion of 1 of the clones into the pGEMEX-1 vector. Only serum from patients with Addison's disease and type 1 polyendocrine autoimmunity syndrome that reacted with the 55 kDa adrenal protein recognised the recombinant 17 alpha-hydroxylase protein on immunoblotting. Our results show that one of the key enzymes in steroid biosynthesis, 17 alpha-hydroxylase, is an autoantigen involved in the pathogenesis of adrenocortical failure.

Addison Disease↗
PubMed1991

Autoimmune reactions to gastric mucosa in chronic gastritis: a review.

The main results of two-decade co-operation between Tartu University, Estonia, and the University of Helsinki, Oulu and Tampere in Finland on immunology of chronic gastritis are presented. These results include data on cell-mediated and humoral immunity to autoantigens from gastric antrum and corpus mucosa in chronic gastritis, gastric ulcer, gastric carcinoma and other gastric diseases, as well as in random samples from two populations.

Autoantibodies↗
PubMed1991

Helicobacter pylori: histological and serological study on gastric and duodenal ulcer patients in Estonia.

We have examined the occurrence of Helicobacter pylori (HP) infection in 86 Estonian gastric ulcer (GU) and 25 duodenal ulcer (DU) patients. Diagnosis of the HP infection was made histologically (modified Giemsa) from gastric biopsy specimens, and serologically by parallel use of two enzyme-linked immunosorbent assays for IgG antibodies to HP in patient sera. The infection was diagnosed simultaneously by all three methods in 84% of the GU and 84% of the DU patients. The infection was revealed histologically in 88% of the GU and 92% of the DU patients, and serologically by either of the two methods in 94% and 92% of the GU and DU patients, respectively. HP infection was absent by all three methods in one GU patient only, this patient being the only subject who showed normal gastric mucosa in conventional histology. These observations show that HP infection is very common in patients with peptic ulcer in Estonia. In addition, the findings suggest that the serological assays will find a small proportion (15%) of ulcer patients with antibodies against HP but no histologically detectable bacteria.

Adult↗
PubMed1991

Alpha 1-antitrypsin allo- and phenotypes in gastric and duodenal ulcer.

Serum alpha 1-antitrypsin (A1AT) allo- and phenotypes (including M1, M2 and M3 alleles) were studied in 99 patients with gastric ulcer (GU) and 56 patients with duodenal ulcer (DU) using agarose isoelectric focusing. The results were compared with the A1AT data of a random population sample of similar genetic background (1422 persons). An increase in M2 allotype and M1M2 phenotype as well as a decrease in Z allotype of A1AT was seen in GU in comparison to DU and the random population. There were no particular clinical features which would distinguish patients with M2 allotype from the remainder of the GU group. However, a trend toward elevated serum pepsinogen I and II levels in patients with M2 allotype was seen. When the pepsinogen levels were compared in the GU patient groups with and without M2 allotype, matched between themselves by the state of the gastric mucosa, a statistically significant difference was revealed between pepsinogen II levels in these two groups. No associations were found between DU and any of the A1AT phenotypes.

Adult↗
PubMed1991

Chronic gastritis: progression of inflammation and atrophy in a six-year endoscopic follow-up of a random sample of 142 Estonian urban subjects.

To study the prevalence and course of chronic gastritis (CG), 142 adult subjects collected at random from an Estonian urban area were endoscopically and bioptically examined at a six-year interval. The histology of the antral and corpus mucosae was evaluated by grading gastritis without ("superficial gastritis"; SG) and with atrophy ("atrophic gastritis"; AG) into mild, moderate and severe categories. A total of 135 (95%) and 139 (98%) subjects showed CG in the 1st and 2nd examinations, respectively. The CG healed in one subjects (0.7%), and in 5 out of 7 subjects with normal stomach in the 1st examination the CG started during the follow-up. No change in the severity of CG was seen in 24% of subjects with gastritis in the 1st examination. The main trend of CG was a slow, "one-step progression" in severity of inflammation and appearance of atrophy and intestinal metaplasia. Inflammation progressed significantly, especially in the young age groups and in the antrum in particular. The prevalence of AG increased linearly with age in corpus (mean annual risk 1.25%). Parietal cell antibodies (PCA) were found in 2 subjects in the 1st examination, and a further 2 subjects developed these antibodies later. Three of four PCA-positive subjects belonged to a subgroup of 8 elderly subjects who had corpus AG at both examinations and who also showed normal or normalizing mucosa in the antrum. It is concluded that CG is a slowly progressive disease advancing with time and, once started, rarely healing spontaneously.

Adolescent↗
PubMed1991

Grade of Helicobacter pylori colonisation in relation to gastritis: a six-year population-based follow-up study.

The prevalence and density of Helicobacter pylori (HP) colonisation was assessed twice, with an interval of six years from antral and corpus biopsies from a randomly collected Estonian urban population sample. Positive HP colonisation was found in either at 1st or 2nd or in both examinations in 85 out of 86 subjects in whom gastritis without atrophy (chronic inflammation without atrophic changes, SG) either developed or remained during the follow-up at the SG level. There was a clear intraindividual tendency to keep the grade of HP colonisation at an unchanged level during the follow-up: the hypothesis of random variation of HP colonisation during follow-up could be statistically rejected. Close to half of the subjects had at both examinations an identical grade of HP colonisation in the antral or corpus mucosa. Distinct changes in HP colonisation were observed in three instances: (1) the appearance of HP colonisation occurred concomitantly with appearance of gastritis; (2) the development of antrum atrophic gastritis (AG) occurred with concomitant diminution and eventual disappearance of HP in the antral side, and (3) normalization of antral mucosa occurred with persistence of corpus AG with concomitant disappearance of HP colonisation at both sites of the stomach mucosa. The grade of HP colonisation increased with increase in severity of SG and decreased with the progression of AG changes. In the antrum at the SG level a distinct increase was seen both in the grade of HP colonisation and in the severity of SG up to middle age, but in the corpus mucosa only HP colonisation but no SG progression was seen in the younger age-groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Inhibition of enzyme function by human autoantibodies to an autoantigen pyruvate dehydrogenase E2: different epitope for spontaneous human and induced rabbit autoantibodies.

Antibodies to the mitochondrial autoantigen M2, characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC), react with the E2 subunit of the pyruvate dehydrogenase enzyme (PDH-E2). We examined the effect of disease sera on the enzyme activation catalysed by the PDH complex. Inhibition of enzyme activity was observed in 19 of 24 sera of patients with PBC with a level of greater than 90% inhibition in 14 at a serum dilution of 1/50. The onset of inhibition by serum was rapid, within the time of mixing, and the inhibitory activity was shown to reside in the immunoglobulin fraction of the serum. The immunoglobulin fraction of control sera from patients with other liver diseases (n = 26) and healthy persons (n = 8) failed to produce inhibitory activity. In addition sera from four rabbits, intensively immunized with a recombinant human M2 autoantigen, gave anti-M2 reactions by fluorescence, ELISA and immunoblotting, but did not inhibit the activity of PDH. The failure of experimentally induced M2 antibodies in rabbits to inhibit is interesting in view of the reactivity of the natural M2 autoantibodies of PBC with the highly conserved site on the enzyme which carries the essential lipoic acid cofactor.

Animals↗
PubMed1989

Relation of parietal cell and thyroid antibodies to the state of gastric mucosa and basal serum gastrin levels during a 6-year follow up.

Two groups of volunteers (199 in total, 149 of whom were a random sample of an urban population) were examined twice, with a 6-year interval, for the occurrence of parietal cell antibody (PCA) and thyroid microsomal antibodies (TMA). The antibody findings were compared with the antral and fundal gastric mucosal state, and with the fasting serum gastrin-17 level. During the study period, two new PCA and four new TMA cases appeared. There were no significant changes in the state of gastric antral/fundal mucosa in relation to PCA and/or TMA persistence or appearance, as compared with the gastric mucosa changes in the whole random population sample. However, a good correlation was observed between PCA and basal serum gastrin elevation.

Adult↗
PubMed1985

Seven-year follow-up study of chronic gastritis in gastric ulcer patients.

The course of chronic gastritis in the antrum and body was followed up for 7 years in 112 patients with gastric ulcer (GU). As controls served 155 subjects collected at random from the same geographical area. At the start of the study (first examination) there was a slight predominance of antrum gastritis in the series, but during the follow-up period (second examination at 4 years (61 out of 112 patients) and third examination at 7 years (39 out of 112 patients] a distinct body gastritis gradually predominated in GU patients. The healing tendency of active ulcer was accompanied by a more pronounced progression of body gastritis. The rate of body gastritis progression was very rapid and was calculated to be 11-fold as compared with that in the population at large. No immunological phenomena were associated with the body atrophy process.

Adult↗
PubMed1985

Immunohistochemical localization of human liver specific protein using rabbit antisera and the avidin-biotin complex technique.

A sensitive enzymatic avidin-biotin complex technique was utilized to locate the antigenic sites in human liver which react with rabbit antibodies to human liver specific protein (LSP). Depending on the rabbit antiserum used, anti-LSP reactive material was seen in different locations. (1) diffusely distributed in liver parenchymal cells, (2) in both hepatocyte cytoplasm and plasma membrane and (3) in hepatocyte plasma membrane only. The cytoplasmic staining was partially or totally abolished by preabsorption with human kidney homogenate whilst the plasma membrane staining remained uninfluenced. The latter was apparently confined to bile canalicular walls and may be liver specific in contrast to the cytoplasmic reaction which seems to be due to antigen determinants cross-reacting with tissue components in kidney.

Animals↗