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Biomedical subjects

J Forster

Publications and source records attributed to J Forster.

At least 91 records · Page 5Linked to original sources
PubMed1997

Predictability of early atopy by cord blood-IgE and parental history.

BACKGROUND: Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. METHODS: A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.

Adult↗
PubMed1997

The natural course of sensitisation and atopic disease in infancy and childhood.

A number of epidemiological studies indicate that the prevalance of allergic airway diseases has been increasing over recent decades, especially in western industrialised countries, for reasons which are not yet completely understood (1, 2, 3). Changes in life style or an increase in indoor allergen exposure due to higher indoor temperature and humidity have been suggested as potential determinants, although evidence for both hypotheses is indirect (4). During the last years we have been following a birth cohort born in 1990 in order to understand the influence of the major genetic and environmental determinants, which are modulating the development of allergic sensitisation and the incidence of atopic symptoms. Sensitisation to indoor allergens has been demonstrated to be one of the major risk factors for the development of asthma in childhood (5, 6, 7, 8). Several cross-sectional studies in older children indicate that specific sensitisation to house dust mites is related to dust mite allergen concentrations in mattress dust (9, 10). Exposure threshold levels for several indoor allergens have been proposed, but individuals vary widely in their susceptibility to levels of exposure, and no absolute value has been identified which could generally ensure minimum risk.

Age Factors↗
PubMed1996

An Mse I RFLP in the human CTLA4 promotor.

We present a PCR-based Mse I restriction fragment length polymorphism (RFLP) in the promotor of the human CTLA4 gene at position -318 relative to the ATG start codon. In a random caucasian population including 239 individuals the allele frequency of the polymorphism was 13.4%, with a calculated heterozygosity rate of 23.2% and an observed one of 25.1%. CTLA4 and CD28 are two genes in close proximity on the long arm of chromosome 2. Both of them influence T-cell activity in an antigen-independent way. They represent candidate genes for several immunological disorders. Recently association between the CTLA4 gene and Graves' disease has been shown. The Mse I RFLP in the CTLA4 promotor might serve as a useful tool for further association studies.

Abatacept↗
PubMed1996

Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver.

Tissue damage in ischemia/reperfusion injury may be mediated by oxidative stress caused by reactive oxidant species. Since such reactive species are difficult to measure directly, changes in antioxidant concentrations are often used as an indication of oxidative stress. In this study, microdialysis membranes were inserted into the livers of anesthetized rats to determine the effects of ischemia/reperfusion on the extra-cellular concentrations of two antioxidants, uric acid and ascorbic acid. Total hepatic ischemia was induced for 30 min by clamping the portal triad and was followed by 60 min of reperfusion. Uric acid and ascorbic acid concentrations were measured in microdialysis perfusates by high-performance liquid chromatography with electrochemical detection. Initial uric acid and ascorbic acid concentrations were high after insertion of membranes into the liver and decreased rapidly within 90 min (P < 0.001; ANOVA with repeated measures). Uric acid concentrations increased over 300% after ischemia and by 600% during the first 30 min of reperfusion (n = 8; P < 0.05). Ascorbic acid concentrations were 60% higher than controls after ischemia and 90% higher during the first 30 min of reperfusion (n = 8; P < 0.05). Alterations in concentrations of these redox-active molecules may be associated with oxidative stress in liver extracellular fluid during ischemia/reperfusion.

Animals↗
PubMed1996

Colonization and infection with Moraxella catarrhalis in childhood.

In a prospective clinical study, rates of isolation of Moraxella catarrhalis in nasopharyngeal aspirates from 122 children with respiratory tract infection and 72 healthy controls were compared. In the patient group, Moraxella catarrhalis and Streptococcus pneumoniae were the most frequently isolated pathogens (38% and 42%, respectively). Monocultures of each pathogen were equally distributed in patients and controls (41% and 42%), whereas mixed infections were found more frequently in the patient group (42% vs 14%; normal flora, 17% vs 44%). Moraxella catarrhalis appears to be a relevant respiratory pathogen. The isolation of two or more pathogens in nasopharyngeal aspirates seems to be as indicative of relevant infection as is monoculture.

Acute Disease↗
PubMed1996

Assessment of the composition of bone marrow prior to and following autologous BMT and PBSCT by magnetic resonance.

Lumbar bone marrow was assessed by means of magnetic resonance (MR) in 23 examinations of eight patients who underwent autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT). Various imaging and spectroscopic techniques were applied for measurements carried out prior to conditioning for ABMT/PBSCT and in the course of reconstitution and correlated with clinical and blood chemistry data in these patients. The signal intensity from lumbar bone marrow was determined in T1-weighted and water- and fat-selective MR images. The distribution of the magnetic field was demonstrated by a field-mapping method. Localized proton spectroscopy was performed from volume elements of 2 ml located in the central region of vertebral bodies in order to evaluate the fraction of the water signals, the transverse relaxation times T2 of the signals from water and lipids, and the line widths of the spectral signals. Regions of bone marrow after inflammatory conditions or intensive irradiation are shown to be not involved in marrow reconstitution. Additional information about marrow composition was obtained by the magnetic field mapping and by the line widths in the spectra. Considerable alterations of the amount of paramagnetic hemosiderin were revealed following transplantation. Patients with low water signal and strong local inhomogeneities of the magnetic field in the marrow prior to transplantation had a delayed hematopoietic reconstitution compared with the patients lacking these MR features.

Adult↗
PubMed1996

Significance of lymph node metastases in patients with pancreatic cancer undergoing curative resection.

BACKGROUND: Recent reports suggest an improved survival following resection for patients with pancreatic carcinoma. However, the prognosis for patients with lymph nodes metastases remains uncertain. The purpose of this study was to determine if the presence of lymph node metastases significantly alters survival in patients with otherwise potentially curable pancreatic carcinoma. PATIENTS AND METHODS: Between 1970 and 1995, 401 patients with pancreatic adenocarcinoma, including 327 patients with pancreatic head tumors, were evaluated and treated. RESULTS: One hundred (31%) patients underwent pancreatoduodenectomy. Operative mortality was 3% and morbidity was 22%. Median survival for 97 patients discharged from the hospital following resection was 14 months (range 2 to 293). The estimated 1-, 2-, and 5-year survivals were 61%, 43%, and 20%, respectively. Median survival was 11.5 months (range 2 to 87) for patients with positive lymph nodes (n = 56) and 24 (range 0 to 293) months for patients with negative lymph nodes (n = 41; P = 0.0003). Ten patients (10%) survived longer than 5 years, and 9 (90%) of them had negative lymph nodes. Elderly patients (> or = 70 years) had a median survival twice as long as younger patients (24 versus 12 months, P = 0.03). CONCLUSIONS: Lymph node metastases are found in 56% of patients undergoing resection. Pancreatoduodenectomy can be performed with low operative mortality in patients of all ages. It offers good palliation for patients with lymph nodes metastases and encouraging long-term survival rates as well as a chance for cure in patients with negative lymph nodes.

Adenocarcinoma↗
PubMed1996

Is the role of transjugular intrahepatic portosystemic shunts limited in the management of patients with end-stage liver disease?

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) are an established method for the treatment of the complications of portal hypertension. Recent reports have suggested that TIPS require frequent follow-up and may interfere with orthotopic liver transplantation (OLT). METHODS: Retrospective chart review was performed of ultrasound studies, angiographic studies, and complications of the first 100 patients treated consecutively with TIPS from February 1992 through October 1995. RESULTS: Ninety-seven patients had functional TIPS. Thirty-one percent of patients treated emergently survived, significantly less than the 96% survival of elective patients. Fifty percent of the shunts were found to require angioplasty by 5 months. Seventeen patients treated with OLT did well, without intraoperative bleeding problems, and are alive. CONCLUSIONS: The TIPS method treats successfully the complications of portal hypertension but requires careful follow-up. The technique may be used prior to OLT. For non-OLT candidates, the cost effectiveness of TIPS versus surgical shunting remains in question.

Adolescent↗
PubMed1996

The cold sensitivity of a mutant of Saccharomyces cerevisiae lacking a mitochondrial heat shock protein 70 is suppressed by loss of mitochondrial DNA.

SSH1, a newly identified member of the heat shock protein (hsp70) multigene family of the budding yeast Saccharomyces cerevisiae, encodes a protein localized to the mitochondrial matrix. Deletion of the SSH1 gene results in extremely slow growth at 23 degrees C or 30 degrees C, but nearly wild-type growth at 37 degrees C. The matrix of the mitochondria contains another hsp70, Ssc1, which is essential for growth and required for translocation of proteins into mitochondria. Unlike SSC1 mutants, an SSH1 mutant showed no detectable defects in import of several proteins from the cytosol to the matrix compared to wild type. Increased expression of Ssc1 partially suppressed the cold-sensitive growth defect of the SSH1 mutant, suggesting that when present in increased amounts, Ssc1 can at least partially carry out the normal functions of Ssh1. Spontaneous suppressors of the cold-sensitive phenotype of an SSH1 null mutant were obtained at a high frequency at 23 degrees C, and were all found to be respiration deficient. 15 of 16 suppressors that were analyzed lacked mitochondrial DNA, while the 16th had reduced amounts. We suggest that Ssh1 is required for normal mitochondrial DNA replication, and that disruption of this process in ssh1 cells results in a defect in mitochondrial function at low temperatures.

Amino Acid Sequence↗
PubMed1996

Bioelectrical impedance in the clinical evaluation of liver disease.

Liver disease is often characterized by an accumulation of excess body water as ascites, edema, or both. It was our purpose, using bioelectrical impedance analysis (BIA), to measure total body water (TBW) and extracellular water (ECW) in 35 patients with end-stage liver disease, including those undergoing orthotopic liver transplantation and, in 15 of these patients, to compare these values with measurements of TBW by deuterium oxide and of ECW by bromide dilutions. Poor correlation of TBW derived from BIA with TBW by deuterium dilution was found (r = 0.36, P = 0.35). In 19 patients, in whom TBW and ECW were not measured by dilution studies, 158 BIA measurements were taken for determining TBW. In 15 orthotopic liver transplantation patients with various amounts of fluid overload, a modest correlation was found between short-term weight change and BIA (r = 0.38, p = 0.001). In patients with fluid overload not exceeding 25% of ECW, ECW correlated with reactance (r = -0.96, P = 0.0025). TBW and ECW were covariant (r = 0.68, P = 0.01). In three patients with cirrhotic ascites, impedance measurements were taken with source electrodes on the hand and foot and detector electrodes on the abdomen during paracentesis of 8-11 L. Calculated volume of ascites correlated with measured volume (r = 0.99, P = 0.001). Segmental electrode placement and parallel impedance measurements were effective in determining ascites fluid volume.

Adult↗
PubMed1996

Allergenic epitopes of bovine alpha S1-casein recognized by human IgE and IgG.

B-cell epitopes of bovine alpha S1-casein, one of the major allergens of cow's milk, were identified by a screening method based on synthetic peptides. According to the known amino acid sequence of alpha S1-casein, a set of 188 overlapping sequential decapeptides shifted by one amino acid was manually synthesized on polyethylene pins by the 9-fluorenyl-methoxycarbonyl (Fmoc) method. Peptides were screened by an enzyme-linked immunosorbent assay (ELISA) specific for human IgE and IgG. Bound antibodies were detected by successive incubation with up to three polyclonal antibodies, the last one conjugated to horseradish peroxidase. Tested sera were from 15 patients with acute clinical reactions to cow's milk and IgE-specific reactions to bovine alpha-casein in the ELISA and immunoblot. Sera from 10 healthy subjects without remarkable reactions to cow's milk proteins were used as controls. All sera from allergic subjects showed reactions with three regions of alpha S1-casein, corresponding to amino acids 19-30, 93-98, and 141-150. Furthermore, individual sera showed reactions with other parts of the protein. No essential differences in the epitope specificity of IgE and IgG were found. Inhibition of IgE binding to alpha S1-casein with soluble synthetic peptides confirmed the results and revealed peptide CN-2 as the most inhibiting one.

Adolescent↗
PubMed1996

Mite allergy, clinical atopy, and restriction by HLA class II immune response genes.

From a community-based study cohort of 1812 elementary schoolchildren we selected 129 unrelated participants to investigate the relevance of HLA-class II molecules (DPB, DQB, and DRB) to the regulation of immune response to the mite allergen Der p 1 and to clinical atopic disorders. On the basis of skin prick test results validated by measurement of specific IgE, individuals were selected and divided into three groups: group I (n = 20), controls without detectable specific IgE to common inhalant allergens; group II (n = 22), children sensitized only to non-mite allergens; group III (n = 85), children sensitized to Der p 1. Clinical history of asthma, eczema, and hay fever was ascertained using standardized questionnaires. In total, 43 different HLA class II alleles (DPB, n = 19; DQB, n = 14; and DRB, n = 10) were determined by sequence-specific oligonucleotide typing with PCR-amplified DNA. We were not able to demonstrate significant differences in gene frequencies of any HLA class II allele between the group of mite-sensitized children and one of the other two groups. However, the presence of certain DRB- and DPB-haplotypes (DRB *0100/*0300/*1100 and DPB *0201/*0401) was significantly associated (p < or = 0.01) with a history of asthma, hay fever, and atopy (defined as a history of asthma and/or hay fever and/or eczema). Other haplotypes, including DQB *0303/*0503, DRB *0200/ *0700, and DPB 0402 were negatively associated with a history of eczema, hay fever, and atopy (p < or = 0.01). Thus, our findings do not suggest a relevance of HLA-class II molecules to mite allergy; however, some HLA class II haplotypes appear to be predictive of the incidence of atopic disorders.

Allergens↗
PubMed1996

Respiratory syncytial virus infection: its role in aeroallergen sensitization during the first two years of life.

Our aim was to study the influence of infection with the respiratory syncytial virus (RSV) in non-hospitalized infants on sensitization to aeroallergens and the early manifestation of atopy. Six hundred and nine infants from the prospective German Multicenter Cohort Study on Atopy were included, 38% of whom had an elevated atopic risk. RSV IgG and IgM antibodies were tested by ELISA with gradient purified RSV antigen. Specific IgE against mites, cat dandruff, birch and grass pollens and relevant nutritional antigens were tested with CAP-RAST-FEIA (Pharmacia, Sweden). Of the cord sera 99% were positive for RSV-IgG, 44.7% at one year and 64.2% (n = 265) at two years of age. The positivity rate after 12 months varied with the season of birth, the number of siblings and the degree of exposure to tobacco smoke; and correlated closely with attacks of wheezing during infancy. Twenty (2.8%) children were found to be sensitized against at least one aeroallergen at one year, and 28 (10.5%) at two years. By the first birthday, mite sensitization (n = 3) could only be seen in the RSV-infected children; grass pollen sensitization (n = 9) was associated with RSV seropositivity (logistic regression model including the confounders mentioned above: with RSV IgG < p = 0.048 > and IgM < p = 0.0006 >), as was birch sensitization (n = 5) with RSV IgM (p = 0.009). No such differences could be detected at two years. No correlation of RSV seropositivity to any allergic manifestation could be found. We conclude, that it is only in the first year of life, that RSV infection plays a significant role in promoting sensitization against aeroallergens, which do not at this time produce allergic symptoms.

Air Pollutants↗
PubMed1996

MxA protein in infants and children with respiratory tract infection.

MxA protein--a stable product of cells stimulated by type I interferons--was examined prospectively for its ability to discriminate between viral and bacterial respiratory tract infections (RTIs) in 182 infants and children. The nasopharyngeal secretions (NPSs) of all of them were tested for MxA using enzyme-linked immunosorbent assay (ELISA), and the whole blood of 92. Seventy-three children undergoing elective surgery served as controls. These apparently healthy children had higher levels of serum MxA than adult controls. Using antigen detection and serology, a viral aetiology was diagnosed in 81/182 cases. The sensitivity and specificity of MxA ELISA were assessed at 92 and 76% for the blood test and at 40 and 91% for the NPS, respectively. The positive predictive value for a viral RTI was superior to a leucocyte count or C-reactive protein when determined only once.

Adult↗
PubMed1996

Specific IgE and IgG4 immune responses to tetanus and diphtheria toxoid in atopic and nonatopic children during the first two years of life.

BACKGROUND: In order to investigate, whether atopic and nonatopic children show differences in their specific IgE and IgG4 immune responses to tetanus (T) and diphtheria (D) antigens, we studied 538 children who had been followed from birth on and from whom records had been kept of all immunizations. METHODS: The prevalence of eczema and asthma was registered at regular intervals and the cumulative incidence of symptoms was determined at 24 months of age. Total serum IgE and specific IgE to a panel of nine allergens as well as T- and D-specific IgE and IgG4 were determined from the 24-months blood samples. RESULTS: Our results show that both atopic and nonatopic children are capable of mounting high levels of toxoid-specific IgE antibody responses. Children with cord blood IgE > 0.9 kU/1, serum IgE 10-100 kU/1 and > 100 kU/1 and at least one sensitization to an allergen at 24 months of age have significantly higher IgE responses to T and D (p < 0.001). In contrast, specific IgG4 antibody concentrations to T and D were not significantly different in children with elevated total IgE levels at 24 months. No differences in subgroups of children with or without early symptoms of atopy were observed. CONCLUSIONS: Our data indicate that IgE responses to toxoids such as T and D are not limited to infants with clinical manifestations of atopy in the first 2 years of life but are related to immunological parameters of atopy.

Asthma↗