Search PubMed⌕ Search

Biomedical subjects

H Baum

Publications and source records attributed to H Baum.

At least 37 records · Page 2Linked to original sources
PubMed1997

An assessment of DNA contamination risks in New York City Medical Examiner facilities.

DNA evidence holds an important position in criminal investigations and proceedings. The polymerase chain reaction (PCR) is often utilized to amplify polymorphic regions of DNA which are subsequently typed to produce distinct genotypes. The sensitivity of PCR-based techniques provides a major advantage over other DNA or conventional serological typing systems. Samples containing quantities of DNA in the picogram range are often typed. However, the unprecedented sensitivity of PCR is often cited as a criticism. One concern is that the interpretation of PCR typing can be affected by DNA contaminants from foreign sources. In this report, the level of DNA contamination in New York City Medical Examiner facilities and its potential affects on HLA-DQA1 typing were assessed. Two related studies conducted over a five week period measured and typed HLA-DQA1 from accumulated DNA on autopsy room and Forensic DNA Laboratory structures. The potential for DNA contamination from airborne sources was also evaluated in the autopsy suites. This study demonstrated the presence of small amounts of DNA on structural surfaces, but little evidence of airborne DNA contamination.

Air Pollutants↗
PubMed1997

MHC-derived peptides and the CD4+ T-cell repertoire: implications for autoimmune disease.

The receptor repertoire of peripheral CD4+ cells is primarily determined by selection processes in the thymus. These result in the positive selection of T cells whose receptors weakly recognize self-peptides restricted by class II self-MHC heterodimers. A majority of such self-peptide partial agonists are likely to be derived from self-MHC molecules. It is suggested that these thymically selected, weakly autoreactive T cells may subsequently be stimulated by peripheral exposure to microbially derived agonists that 'mimic' corresponding self-MHC peptides. In turn, 'molecular mimicry' between microbial agonists and tissue-specific self-peptides may lead to T-cell-mediated autoimmune disease. Hence such disease may reflect 'three-way mimicry' between peptides of respectively target tissue, pathogen and self-MHC (or other self-peptide dominantly presented in the thymus). This hypothesis accounts for the role of MHC haplotype in determining susceptibility to (or protection from) autoimmune disease. Direct evidence is presented in favour of the model as applied to diseases such as rheumatoid arthritis, autoimmune uveitus and autoimmune diabetes. Strong circumstantial evidence, based primarily on sequence similarities, is also presented for other autoimmune diseases. However, it is noted that the statistics of database searches, and the lack of predictable correlation between sequence similarity and T-cell cross-reactivity, require that such evidence be substantiated by further direct experiment.

Alleles↗
PubMed1997

Multicenter evaluation of a second-generation assay for cardiac troponin T.

We report on the evaluation of the second-generation assay for cardiac troponin T (cTnT) on the Enzymun system. This new assay is completely specific for the cardiac isoform of TnT, utilizing two cardiospecific monoclonal antibodies. The assay time is reduced to 45 min. The interassay precision shows a median CV of 5.5%; 20% interassay CV was found between 0.05 and 0.1 microg/L. The cardiosensitivity of the second-generation cTnT assay in patients with ischemic myocardial injury appears equivalent when compared with the first-generation assay. We found no falsely positive results in patients with skeletal muscle damage including multitraumas, surgery patients, and marathon runners who showed highly increased values with the unspecific first-generation assay. In Duchenne disease cTnT was still increased, but to a much lower extent. cTnT remains increased in renal failure, but to a lesser degree than with the first-generation assay. The cause of this increase remains unclear. Although a cross-reactivity of skeletal muscle TnT in the second-generation assay could be excluded by our findings, minor myocardial damage or expression of the cardiac isoform of TnT in regenerating muscles cannot be ruled out in those cases with apparently falsely increased cTnT values. The second-generation cTnT assay is a step forward in the combination of cardiosensitivity and cardiospecificity in biochemical markers for diagnosis of heart disease.

Artifacts↗
PubMed1996

Resolution of apolipoprotein B repeat unit position variants on agarose, denaturing, and native polyacrylamide gels.

Utilizing three different electrophoresis systems for the separation of variable number of tandem repeats (VNTR) alleles of the high variable region 3' from the apolipoprotein B (Apo B) locus, it could be shown that apparent allele subtypes on native polyacrylamide gels comigrated with the regular ladder alleles on agarose and denaturing polyacrylamide gels. Two subtypes, one with a shift towards the cathode and one shifted towards the anode, and the corresponding ladder alleles were sequenced in order to determine the molecular basis for this aberrant electrophoretical mobility. Subtype and ladder alleles displayed the same number of repeat units but differed in the number and order of different types of repeats. Depending on the variation in the region of pure AT repeat units, the potential secondary structures of hairpin loop formation differed for subtypes and ladder alleles, which is thought to explain the shift in electrophoretic mobility on native polyacrylamide gel electrophoresis.

Apolipoproteins B↗
PubMed1996

Molecular mimicry in the MHC: hidden clues to autoimmunity?

The term 'molecular mimicry' has been used to describe a spectrum of antigenic crossreactivities thought to underlie autoimmune disease. For T-cell crossreactivities to occur, appropriate T-cell clones must be available. Here, Harold Baum, Huw Davies and Mark Peakman speculate that an important source of self-peptides that govern thymic selection of such clones are MHC molecules themselves.

Amino Acid Sequence↗
PubMed1996

Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa.

Significant osteoporosis affects over half of all women with anorexia nervosa (AN). The mechanisms of bone loss in this condition are not known, and estrogen administration alone has not been shown to prevent bone loss. Insulin-like growth factor I (IGF-I), a nutritionally dependent bone trophic hormone, is know to stimulate osteoblast function and collagen synthesis in vivo and in vitro. We hypothesized that short term administration of recombinant human IGF-I (rhIGF-I) would increase bone turnover in young women with AN. We studied 23 women, aged 18-29 yr (mean +/- SD, 23 +/- 4 yr) with AN. Spinal bone density was significantly reduced compared to that in age-matched controls (0.85 +/- 0.11 vs. 1.19 +/- 0.12 g/cm2 by dual energy x-ray absorptiometry; P < 0.001) and was below the normal mean in 54% of the women. Patients were randomized to receive rhIGF-I (100 or 30 micrograms/kg) or placebo sc twice a day for 6 days. Bone turnover was assessed at baseline and after 3 and 6 days of treatment using two markers of bone formation [osteocalcin (OC) and type I procollagen carboxyl-terminal propeptide (PICP)] and three specific markers of bone resorption [pyridinoline (PYRX), deoxypyridinoline (DPYRX), and N-telopeptide (NTX)]. Serum OC was reduced significantly (P < 0.001) in women with AN compared to normal premenopausal women (5.4 +/- 3.8 vs. 8.6 +/- 4.5 ng/mL) and correlated with percent fat mass (r = 0.60;P < 0.01) and body mass index (r = 0.50;P < 0.05). Markers of bone resorption were elevated significantly compared to normal levels [DPYRX, 18.2 +/- 7.0 vs. 11.4 +/- 5.2 nmol/mmol creatinine, (P < 0.001); NTX, 53.5 +/- 22.5 vs. 36.5 +/- 14.6 nmol BCE/mmol creatinine (P < 0.01)]. IGF-I levels were relatively low at baseline compared to those in age-matched controls (203 +/- 93 vs. 262 +/- 84 ng/mL;P < 0.01) and increased to 673 +/- 268 ng/mL [P < 0.05; 100 micrograms/kg twice daily (BID)] and 545 +/- 255 ng/mL (P < 0.05; 30 micrograms/kg BID). During short term administration of rhIGF-I at a dose of 100 micrograms/kg BID, there was a significant (P < 0.05) increase in markers of bone formation, as assessed by both PICP (147 +/- 33 to 303 +/- 187 ng/mL) and OC (5.3 +/- 3.8 to 10.9 +/- 7.4 ng/mL). There was also a significant (P < 0.05) increase in markers of bone resorption as assessed by PYRX (51.0 +/- 16.6 to 87.1 +/- 8.2 nmol/mmol creatinine) and DPYRX (17.3 +/- 4.5 to 26.3 +/- 3.7 nmol/mmol creatinine). The group randomized to receive short term administration of rhIGF-I at a dose of 30 micrograms/kg BID demonstrated a significant (P < 0.05) increase in PICP (110.9 +/- 47.0 to 134.8 +/- 43.2 ng/mL) and an insignificant increase in OC levels (4.5 +/- 3.2 to 6.8 +/- 5.9 ng/mL). However, markers of bone resorption were unchanged during rhIGF-I administration at this dose. Serum PTH and serum and urinary calcium were unchanged in both treatment groups compared to placebo levels. These data demonstrate that young women with anorexia nervosa have decreased markers of bone formation and increased bone resorption. This is the first demonstration that short term rhIGF-I administration increases markers of bone turnover in severely osteopenic women with AN. The effects of short term rhIGF-I on bone turnover are dose dependent. At a dose of 100 micrograms BID, rhIGF-I administration significantly stimulated both markers of bone formation and bone resorption. At a dose of rhIGF-I of 30 micrograms BID, there was an increase in one marker of bone formation, PICP, without a change in markers of bone resorption. Further studies are required to determine whether chronic administration of rhIGF-I can affect bone mass in young women with profound osteopenia due to anorexia nervosa.

Adolescent↗
PubMed1995

Mitochondrial antigens, molecular mimicry and autoimmune disease.

The immune system is normally tolerant to mitochondrial self-antigens, but responsive against bacteria. Low-titre anti-mitochondrial antibodies (AMA) might be involved in this discrimination. Tolerance is broken in diseases characterised by high titre AMA. Some of these AMA, against cardiolipin, cross-react with DNA. The best studied AMA are those characterising primary biliary cirrhosis (PBC). These are directed against E2 subunits of the oxo-acid dehydrogenase complexes, and also against subunits E1 alpha, E1 beta and X of the pyruvate dehydrogenase complex. AMA of PBC patients also react with bacterial E2s. Reactivities are primarily peptide-specific but with cross-reactivity between mitochondrial and microbial antigens and between E2s of respective complexes. Immunodominant epitopes, for anti E2 AMA, include the conserved sequence flanking the site of lipoyl attachment. It is proposed that the initial stimulus for antibody production is chronic urinary tract infection. AMA themselves are not pathogenic, but CD4+ T-cells would be primed, recognising the lipoyl domain epitope in association with class II HLA. Inappropriate expression of class II antigens on bile duct epithelia, (as found in PBC), might lead to presentation of a particular fragment of HLA-DR alpha, known to be a major MHC presented self-peptide in the mouse. That sequence strongly mimics the lipoyl domain and might be recognised by primed T-cells, initiating the autoimmune cascade. In the mouse, a peptide of ND1 of Complex I is presented in association with class I MHC. Cells exhibiting somatic mutation of such a peptide might thus be subject to attack by CD8+ T-cells. If such peptides were presented by class II HLA, autoimmune diseases might arise, related to mimicry between such peptides and microbial sequences and/or self-antigens. These considerations might apply in Leber's disease and in age-related pathology.

Animals↗
PubMed1995

Detection of M2 antibodies in patients with recurrent urinary tract infection using an ELISA and purified PBC specific antigens. Evidence for a molecular mimicry mechanism in the pathogenesis of primary biliary cirrhosis?

Primary Biliary Cirrhosis (PBC) is a chronic liver disease of unknown aetiology. The main characteristic feature of the disease is the presence of circulating antimitochondrial antibodies (AMA) to components (collectively named M2) of the mitochondrial 2-oxo-acid multienzyme complexes; pyruvate, oxoglutarate and branched chain oxo-acid dehydrogenase complexes. As these enzymes are phylogenetically conserved, AMA also exhibit reactivity against a range of microorganisms. PBC patients have an increased incidence of recurrent urinary tract infection (UTI) compared to other chronic liver disease controls. Interestingly, we have recently detected low titre AMA in patients with a history of recurrent UTI but normal liver function using crude bovine heart mitochondrial preparations and immunoblotting techniques. Here we confirm these findings using purified M2 antigens and ELISA. We found that 52% of "normal" subjects with a history of recurrent UTI had AMA specifically to M2 antigens. The percentage was significantly higher than that found for chronic liver disease (19%, p < 0.01) and normal controls (4%, p < 0.001). These results support our hypothesis for molecular mimicry in PBC. We propose that a bacterial trigger, possibly resulting from recurrent UTIs, is responsible for initiating an autoimmune response in a predisposed host because of a cross-reactivity between mitochondrial and bacterial antigens.

Antibody Specificity↗
PubMed1994

A rapid assay for the quantification of myoglobin: evaluation and diagnostic relevance in the diagnosis of acute myocardial infarction.

We evaluated a new, fast, quantitative, turbidimetric assay (TurbiTimeSystem, Behringwerke AG, Marburg, Germany) for the determination of myoglobin concentration in serum. Within-run imprecision (n = 10) was < 3.7% in controls ranging from 81.1 to 621.4 micrograms/l and between-day imprecision (n = 50) was < 6% in controls ranging from 69.5 to 623.4 micrograms/l. The assay is linear over the measuring range and interfering substances such as bilirubin, haemoglobin or haptoglobin do not interfere but triacylglycerol-rich samples are only measurable after brief ultracentrifugation. EDTA- or citrate-treated samples display depressed myoglobin concentration when compared with serum samples. The upper reference limit for apparently healthy individuals (n = 100, 50 female and 50 male) is 61.5 micrograms/l. Comparison with nephelometry revealed a good correlation (r = 0.982) between the two methods with the regression equation: turbidimetric assay = 5.53 + 1.02x nephelometric assay. Serial determination of myoglobin concentration and creatine kinase in 18 patients with proven acute myocardial infarction showed in general an equal diagnostic significance for both analytes. In the first 4 hours after onset of chest pain, the determination of myoglobin can have an advantage, since it is released into the blood stream at an earlier stage, but thereafter myoglobin can lead to false negative diagnosis. Therefore, determination of creatine kinase and its isoenzyme MB is still the diagnostic strategy of choice in the diagnosis of acute myocardial infarction.

Citrates↗
PubMed1993

Autoimmune disease and molecular mimicry: an hypothesis.

Helper T lymphocytes are normally only stimulated to initiate an immune reaction through the recognition of peptides bound to class II major histocompatibility complex (MHC) molecules. Class II MHC molecules are constitutively expressed on antigen-presenting cells which play a critical role in the initiation of immune responses. In disease states, however, other cells often express class II MHC molecules inappropriately. This article suggests an hypothesis for the pathogenesis of autoimmune diseases based on molecular mimicry. The mimicry described is between microbial or viral peptides presented by antigen-presenting cells and self peptides presented inappropriately on a target tissue. This leads to helper T cells, stimulated by peptides derived from infectious organisms, initiating an autoimmune attack on the target tissue.

Amino Acid Sequence↗