Biomedical subjects

J Bertrams

Publications and source records attributed to J Bertrams.

At least 19 recordsLinked to original sources

PubMed1997

Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease.

Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies (ICAs) in IDDM patients were associated with high levels of Th1 and Th2 cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. Also, HLA-DQ types did not significantly correlate with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory cytokines appeared to be the most reliable marker of the individual disease process. This study provides first evidence of a systemic bias in the immune regulation of humans, which might be either toward cell-mediated immunity (Th1) in IDDM or humoral immunity (Th2) in Graves' disease.

Adolescent↗

PubMed1995

Circulating forms of ICAM-3 (cICAM-3). Elevated levels in autoimmune diseases and lack of association with cICAM-1.

The intercellular adhesion molecule-3 (ICAM-3) has been identified as the third LFA-1 ligand in addition to ICAM-1 and ICAM-2. In this report we have identified circulating forms of ICAM-3 (cICAM-3) in human serum. Using a sandwich ELISA with two monoclonal anti-ICAM-3 Abs, we detected cICAM-3 in concentrations between 40 and 360 ng/ml in all of 112 healthy controls. An analysis of patient sera from 10 different immune-mediated diseases revealed a distinct pattern of expression. Significantly elevated cICAM-3 levels were found in rheumatoid arthritis, systemic lupus erythematosus, Guillain-Barré syndrome, and multiple sclerosis, but not in type I diabetes, Grave's disease, chronic autoimmune thyroiditis, ulcerative colitis, or Crohn's disease. cICAM-3 levels were significantly higher in systemic lupus erythematosus patients with active compared with nonactive disease. Despite their binding to the same integrin receptor, serum levels of cICAM-3 did not correlate with cICAM-1 concentrations in either normal persons or in patients. The majority of patients had either elevated cICAM-3 or cICAM-1 levels but not both. In conclusion, a circulating form of ICAM-3 is present in human sera. cICAM-3 expression is elevated in certain immune-mediated diseases but occurs independently of cICAM-1.

Adolescent↗

PubMed1995

Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis.

Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA69 and maltose binding protein. ICA69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA69 antibody titres were 3.4 (+/- 1.4) in 99 patients with acute IDDM compared to 2.8 (+/- 0.9) in 49 healthy blood donors (p < 0.001). A higher mean ICA69 antibody titre of 4.1 (+/- 0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p < 0.01) and healthy control subjects (p < 0.001). The percentage of sera with ICA69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n = 20), inflammatory bowel disease (n = 9) or multiple sclerosis (n = 7) had elevated ICA69 antibodies. In IDDM, presence of ICA69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Intragastric acidity as a predictor of the success of Helicobacter pylori eradication: a study in peptic ulcer patients with omeprazole and amoxicillin.

Omeprazole plus amoxicillin cures Helicobacter pylori infection. The hypothesis was tested that low acidity is a predictor of outcome. Fifty patients with relapsing or complicated, or both H pylori positive duodenal (n = 25) or gastric ulcer (n = 25) were randomly treated with either omeprazole 20 mg twice daily plus amoxicillin 1 g twice daily or with omeprazole 40 mg twice daily plus amoxicillin 1 g twice daily over two weeks. After one week of combined treatment, a 24 hour gastric pH measurement was performed in all patients. H pylori cure rate was 67%. Patients who later turned out to be cured had higher pH values during night time and after meals (p < 0.05). In an explorative analysis drug compliance, smoking, location of the ulcer (duodenum versus stomach), age, and grade of body gastritis were additional predictors of the outcome. Smoking (p = 0.006), compliance (p = 0.037), duodenal ulcer disease (p = 0.065), and young age (p = 0.021) were related to high acidity. In conclusion, the success of eradication treatment with omeprazole and amoxicillin in ulcer patients infected with H pylori depends on intragastric pH. Drug compliance, smoking habits, location of ulcer, age, and activity of body gastritis are other predictors and in part related to intragastric acidity.

Adult↗

PubMed1995

High-dose omeprazole plus amoxicillin or clarithromycin cures Helicobacter pylori infection in duodenal ulcer disease.

Treatment with omeprazole plus amoxicillin or clarithromycin resulted in encouraging Helicobacter pylori cure rates in pilot and controlled studies. The present prospective, randomized study was designed to compared the efficacy and safety of amoxicillin and clarithromycin as constituents of omeprazole-enhanced antibiotic therapy of H. pylori infection. Fifty patients with active duodenal ulcer disease and histologically and/or culturally confirmed H. pylori colonization of the gastric mucosa were treated with omeprazole (day 1-14: 40 mg twice daily, day 15-42: 20 mg once in the morning). The patients were randomly assigned to receive either amoxicillin (1 g twice daily; group I: n = 25) or clarithromycin (500 mg twice daily; group II: n = 25) during the first 2 weeks of treatment. The patients of group I and II had comparable demographic and clinical characteristics. One patient of group I was lost to follow-up. H. pylori infection was cured in 87.5% of group I and 84.0% of group II (p = 1.00). All ulcers had healed after 6 weeks of omeprazole treatment. Pain relief occurred within the first day of treatment in the majority of patients of both groups (p = 0.89). Minor side effects were recorded in 6 patients of group I and in 4 patients of group II (25 vs. 16%; p = 0.50). In 1 female patient amoxicillin had to be withdrawn after 3 days because of nausea and emesis. In conclusion, 2 weeks of treatment with omeprazole plus amoxicillin or clarithromycin are highly and equally effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.

Amoxicillin↗

PubMed1994

Medium- and high-dose omeprazole plus amoxicillin for eradication of Helicobacter pylori in duodenal ulcer disease.

The purpose of the present study was to investigate the Helicobacter pylori eradication potency of combined amoxicillin-omeprazole treatment in patients with duodenal ulcer disease and to compare the efficacy of two omeprazole and amoxicillin doses concerning H. pylori eradication, ulcer healing, pain relief, and safety. Ninety patients with active H. pylori-positive (culture and/or histology) duodenal ulcer disease were randomly treated with either omeprazole 20 mg twice a day plus amoxicillin 1 g twice a day (group I, N = 30), omeprazole 40 mg twice a day plus amoxicillin 1 g twice a day (group II, N = 30), or omeprazole 40 mg twice a day plus amoxicillin 1 g three times a day (group III, N = 30) over two weeks, followed by ranitidine at bedtime for another four weeks. The overall proportion of H. pylori eradication was 83% and of ulcer healing 92% without statistically significant differences between the study groups. Complete pain relief occurred after a median of one day in all groups. Six patients complained of side effects during the therapy phase, which led to therapy discontinuation in one female patient. In conclusion, omeprazole plus amoxicillin is a highly effective and well-tolerated therapy regimen to eradicate H. pylori in duodenal ulcer disease. In addition, the results suggest that there is no clear dose-response relation between the dosages of omeprazole and amoxicillin used in this study on the one hand and the H. pylori eradication rates on the other.

Adult↗

PubMed1994

Inflammatory islet damage in patients bearing HLA-DR 3 and/or DR 4 haplotypes does not lead to islet autoimmunity.

The hypothesis was tested that islet autoimmunity is induced by ongoing islet cell destruction in subjects with susceptibility genes HLA-DR 3 and/or DR 4. Sixty-one patients with confirmed chronic pancreatitis were analysed, 30 of whom expressed HLA-DR 3 and/or DR 4. Electron microscopy studies in 10 patients showed that the inflammatory process also affected islets, as recognisable from islet cell lysis, intrainsular fibrosis and immune cell infiltrates. None of the sera tested contained any of three markers of islet autoimmunity, ICA, IAA or GAD antibodies. A correlation was seen between the loss of exocrine function, as determined by the ALTAB-test, and of beta-cell function, as determined by the C-peptide response to i.v. glucagon. However, there was no preferential loss of beta-cell function in patients with HLA-DR 3 and/or DR 4. We conclude that islet cell destruction occurs during chronic pancreatitis, but does not trigger islet autoimmunity, even in the presence of HLA-DR 3 and/or DR 4.

Adult↗

PubMed1994

Effective treatment after failure of omeprazole plus amoxycillin to eradicate Helicobacter pylori infection in peptic ulcer disease.

METHODS: Fifty patients with relapsing or complicated Helicobacter pylori positive duodenal (n = 41) or gastric ulcer disease (n = 9) and failure of a combined treatment with omeprazole plus amoxycillin to eradicate H. pylori infection were re-treated with either oral triple therapy (bismuth subsalicylate, metronidazole, tetracycline) plus ranitidine [group I: n = 22] or high-dose omeprazole (40 mg b.d. to t.d.s.) plus amoxycillin (1 g t.d.s.) [group II: n = 28]. RESULTS: Patients of group I and II had similar demographic and clinical characteristics. The overall proportion of eradication of H. pylori infection was 81.8% in group I and 78.6% in group II (P = N.S.) as judged from negative bacterial findings by means of an urease test, specific culture and histology after modified Giemsa stain. Ulcer healing was observed in all patients after a maximum duration of 10 weeks. Ten patients on triple therapy and only one patient on omeprazole plus amoxycillin (45.5% vs. 3.6%; P < 0.001) complained of side effects without necessity of discontinuation of the study medication in either group. Twenty patients (group I: n = 10; group II: n = 10) with relapsing duodenal ulcer disease and successful cure were prospectively followed for one year without any evidence of ulcer relapse or H. pylori re-infection. CONCLUSION: Oral triple therapy plus ranitidine or high-dose omeprazole plus amoxycillin remain highly effective in eradicating H. pylori infection in patients with peptic ulcer disease and treatment failure of omeprazole/amoxycillin, but the omeprazole enhanced antibiotic monotherapy seems to be superior with regard to side effects. Thus, high-dose omeprazole/amoxycillin is recommended as the treatment of first choice in these selected patients. Triple therapy should be reserved for patients intolerant of amoxycillin.

Administration, Oral↗

PubMed1994

Linear loss of insulin secretory capacity during the last six months preceding IDDM. No effect of antiedematous therapy with ketotifen.

OBJECTIVE: To investigate the effect of an antiedematous therapy with the histamine antagonist ketotifen on beta-cell function in late prediabetes. RESEARCH DESIGN AND METHODS: In a randomized double-blind placebo-controlled study, ketotifen was administered for 3 months to 9 islet cell antibody positive (ICA+) prediabetic patients with a first-phase insulin response (FPIR) below the 2.5th percentile to preserve residual beta-cell function. Patients were followed by intravenous glucose tolerance tests (IVGTTs) every 4-6 weeks for determination of FPIR, HbA1, ICAs, and insulin autoantibodies. In 5 patients, the immune activation state was followed by determination of serum levels of tumor necrosis factor-alpha (TNF-alpha), beta 2-microglobulin, and C-reactive protein (CRP). RESULTS: Seven of nine patients developed diabetes within one year of follow-up. Irrespective of treatment with ketotifen, a slow and linear decline (P < 0.05) of 1 + 3-min insulin values was observed in sequential IVGTTs in those 7 patients who developed insulin-dependent diabetes mellitus (IDDM) during follow-up. The 2 other patients showed wide fluctuations of the insulin response with a threefold increase of initial insulin levels. HbA1 did not correlate with FPIR. Fasting blood glucose increased significantly during the study (P < 0.05). Individual levels of serum TNF-alpha, CRP, and beta 2-microglobulin did not change during the study. CONCLUSIONS: The study could not demonstrate preservation of beta-cell function by ketotifen in the late stage before manifestation of clinical diabetes. Manifestation is preceded in the last 6 months by a steady loss of the FPIR without rapid deterioration immediately before diagnosis and without signs of increased immune activity.

Adolescent↗

PubMed1994

Medium- or high-dose omeprazole plus amoxicillin eradicates Helicobacter pylori in gastric ulcer disease.

OBJECTIVE: To compare the efficacy of two omeprazole/amoxicillin regimens concerning Helicobacter pylori eradication, ulcer healing, pain relief, and safety in patients with gastric ulcer disease. METHODS: In a prospective, single-blind, single-center study, 70 patients with active, H. pylori-positive (histology and/or culture) gastric ulcers were randomly treated with either omeprazole 20 mg b.i.d. plus amoxicillin 1 g b.i.d. (group I; n = 35) or with omeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. over 2 wk, followed by full dose ranitidine for another 4 wk. Patients were investigated clinically and endoscopically prior to treatment and after 6 wk, including the assessment of H. pylori status by means of urease test, specific culture, and histology. RESULTS: Patients of group I and II had similar demographic and clinical characteristics. Three patients were lost to follow-up. The overall proportion of H. pylori eradication was 88.1% (group I, 91.2%; group II, 84.8%, p = NS). The ulcer healing rate was 79.1% after 6 wk, 92.5% after 10 wk, and 100% after 6 months, without a statistically significant difference between the study groups. Complete pain relief occurred after a median of 2 days (group I) and 1.5 days (group II, p = NS), respectively. Six patients (9.0%) complained of side effects that led to discontinuation of amoxicillin treatment in three patients (4.5%). CONCLUSIONS: Omeprazole plus amoxicillin is a highly effective and well-tolerated therapy regimen to eradicate H. pylori from the gastric mucosa of patients with gastric ulcer disease. In addition, the results clearly suggest that medium- and high-dose omeprazole schedules are equally effective with regard to bacterial eradication, ulcer healing, pain relief, and safety in gastric ulcers. Thus, medium- and not high-dose omeprazole plus amoxicillin should be the treatment regimen of first choice to eradicate H. pylori in gastric ulcer disease.

Adult↗

PubMed1993

Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation.

Insulin-dependent diabetes was observed in a woman, aged 29, 4 years after transplantation of bone marrow from her HLA-identical brother with insulin-dependent diabetes. Both had classic symptoms and insulin dependency from onset. At diagnosis of diabetes the recipient was positive for high-titre islet cell antibodies (ICA) whereas she had been ICA negative before transplantation. Chromosomal analyses verified that all circulating leucocytes were of male donor type. These findings suggest transfer of insulin-dependent diabetes by bone marrow cells and confirm the immune nature of the disease.

Adult↗

PubMed1992

Apparently non-expressed alleles of factor B (BF) code for hypomorphic proteins.

In three families with an apparent non-expressed factor B (BF) allele (BF*Q0), advanced methods of isoelectric focusing for the determination of BF F subtypes revealed different hypomorphic BF products (BF QL) with functional hemolytic activity expressed by the assumed BF*Q0 allele. A Taq I and a Msp I restriction fragment length polymorphism as well as the Ba fragment of the expression products showed banding patterns for the BF*QL alleles corresponding to BF S types, whereas an altered Bb fragment was seen in two BF QL products. In one family an intragenic recombination site within the Bb part of the BF gene was assumed. Investigations of factor B and its conversion fragments, as demonstrated by the used methods, allow to complement molecular genetic investigations of BF*Q0 alleles in heterozygous genotypes on a protein level. We conclude that apparently non-expressed alleles of factor B code for hypomorphic but functionally active proteins.

Alleles↗

PubMed1992

Biostatistical basis of individualization and segregation analysis using the multilocus DNA probe MZ 1.3: results of a collaborative study.

A collaborative study using the multilocus minisatellite DNA probe MZ 1.3 was carried out to investigate segregation information, mutation rate, DNA fragment frequencies as well as band sharing characteristics. The fingerprint patterns of 393 children as well as 694 unrelated individuals were analysed after digestion of DNA with the restriction enzyme HinfI. A mutation rate of 1% per meiosis or 0.04% per band was found with a mean number of 26 bands/individual. It was shown that maternal and paternal fragments are inherited in equal proportions. Population frequencies of restriction fragments demonstrated a distribution with increasing frequencies in the small fragment size range below 10 kb as well as the absence of very common or very rare fragments. Our data can be used to calculate simple exclusion probabilities based on the number of non-maternal bands in the child.

Biometry↗

PubMed1992

Association of Crohn's disease and multiple sclerosis. Is there a common background?

Crohn's disease (CD) and multiple sclerosis (MS) share familial occurrence and similar epidemiological traits. Apart from one report of both diseases occurring among consanguineous relatives, only three cases of CD and MS in the same patient have thus far been described. We describe here a 29-year-old woman in whom MS developed in 1983 and CD in 1989. The MS may have been the result of a strongly HLA-associated genetic predisposition, while the additional development of CD may have been due either to genetic factors or perhaps simply to chance. Viewing this case in the context of epidemiological data, however, we suggest that the development of CD and MS is based on one or more common genetic factors acting in conjunction with other presumably exogenous factors and triggering HLA antigens to lead to one disease or the other.

Adult↗

PubMed1992

Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM.

Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were > 2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA- individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or-DR4 with the diabetic relative) but not in the HLA-DR3- and/or -DR4- relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM.

Adult↗

PubMed1991

Proinsulin autoantibodies are more closely associated with type 1 (insulin-dependent) diabetes mellitus than insulin autoantibodies.

The disease association of autoantibodies to proinsulin and insulin was compared in patients with Type 1 (insulin-dependent) diabetes mellitus and first-degree relatives. Following the recommendation of the Fourth International Workshop on the Standardization of insulin autoantibodies, autoantibodies were determined by fluid-phase radioimmunoassay using equimolar concentrations of mono-125I-A14-insulin or -proinsulin to detect insulin or proinsulin autoantibodies, respectively. A higher prevalence of proinsulin autoantibodies vs insulin autoantibodies was found in 97 patients with Type 1 diabetes prior to insulin treatment (34.0% vs 22.7%, p less than 0.05) and in 16 islet cell antibody-positive relatives (43.8% vs 31.3%, NS). There was only one serum positive for insulin and proinsulin autoantibodies in 110 islet cell antibody-negative first degree relatives (0.9%). None of 88 normal sera contained proinsulin autoantibodies or insulin autoantibodies. There was a close correlation of proinsulin autoantibody and insulin autoantibody titres in individual sera (r = 0.95, p less than 0.01) due to crossreaction of all insulin autoantibodies with proinsulin. However, some proinsulin autoantibodies did not crossreact with insulin. Background binding in normal sera was lower for proinsulin autoantibodies. We conclude that proinsulin autoantibodies have a higher association to acute Type 1 diabetes than insulin autoantibodies.

Adult↗

PubMed1990

Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus.

The two genes for the C4A and C4B isotypes of the fourth component of human complement are located in the MHC class III region. Previous studies have demonstrated the unusual expression of C4 genes in the form of aberrant or duplicated haplotypes. Null alleles of C4A or C4B (AQ0 or BQ0) have been defined by the absence of gene products and occur at frequencies of 0.1-0.3. However, only some C4 null alleles are due to gene deletions, the remainder were thought to be nonexpressed genes. We have analyzed the C4 gene structure of 26 individuals lacking either C4A or C4B protein. The DNA of individuals with apparently nonexpressed C4 genes was tested for the presence of C4A- and C4B-specific sequences using restriction fragment analysis and isotype-specific oligonucleotide hybridization of DNA amplified by polymerase chain reaction. All nondeleted AQ0 allels had C4A-specific sequences and may thus be described as pseudogenes, whereas the nondeleted BQ0 alleles had C4A-instead of C4B-specific sequences. Gene conversion is the probable mechanism by which a C4A gene is found at the second C4 locus normally occupied by C4B genes.

Alleles↗

PubMed1990

Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type.

Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control.

Autoantibodies↗