Biomedical subjects
H Baum
Publications and source records attributed to H Baum.
Lipoprotein(a) and coronary thrombosis and restenosis after stent placement.
OBJECTIVES: The objective of this prospective study was to evaluate the relation between high lipoprotein(a) levels and thrombotic and restenotic events after coronary stent implantation. BACKGROUND: Lipoprotein(a) may promote atherogenesis, coronary thrombosis and restenosis after balloon angioplasty, but the clinical significance remains unclear. METHODS: The study included 2,223 consecutive patients with successful coronary stent placement. According to the serum level of lipoprotein(a), patients were divided in two groups: 457 patients of the highest quintile formed the high lipoprotein(a) group, and 1,766 patients of the lower four quintiles formed the low lipoprotein(a) group. Primary end points were the incidence of angiographic restenosis at six months and the event-free survival at one year. Secondary end point was the incidence of angiographic stent occlusion. RESULTS: Early stent occlusion occurred in four of the 457 patients (0.9%) with high and 37 of the 1,766 patients (2.1%) with low lipoprotein(a) levels, odds ratio of 0.41 (95% confidence interval, 0.15 to 1.16). Angiographic restenosis occurred in 173 of the 523 lesions (33.2%) in the high lipoprotein(a) group and 636 of the 1,943 lesions (32.7%) in the low lipoprotein(a) group, odds ratio of 1.02 (0.83 to 1.25). The probability of event-free survival was 73.0% in the high lipoprotein(a) group and 74.8% in the low lipoprotein(a) group (p = 0.45). On the basis of the findings in the low lipoprotein(a) group, the power of this study to detect a 25% increase in the incidence of restenosis and adverse events in the group with elevated lipoprotein(a) was 90% and 75%, respectively. CONCLUSIONS: Elevated lipoprotein(a) levels did not influence the one-year clinical and angiographic outcome after stent placement. Thrombotic events and measures of restenosis were not adversely affected by the presence of high lipoprotein(a) levels.
Spontaneous T-cell proliferation in the non-obese diabetic mouse to a peptide from the unique class II MHC molecule, I-Ag7, which is also protective against the development of autoimmune diabetes.
AIMS/HYPOTHESIS: Major histocompatibility complex class II molecules present antigenic peptides to T-cells and have an important role in T-cell thymic education. The mechanism by which major histocompatibility complex alleles confer a high genetic risk for autoimmune diabetes is not known. One hypothesis is that during positive thymic selection, the peripheral T-cell repertoire is modelled by major histocompatibility complex-restricted presentation of self major histocompatibility complex molecule-derived peptides, some of which mimic tissue autoantigens. The sequence similarity between a known T-cell epitope of glutamic acid decarboxylase-65, 509:VPPSLRTLED and the non-obese diabetic mouse class II major histocompatibility complex molecule I-Ag7 86:VPTSLRRLEQ is consistent with this. METHODS: We measured spontaneous proliferation of peripheral T-cells from non-obese diabetic mice and other, non-diabetes-prone strains, to the I-Ag7 86-101 and glutamic acid decarboxylase-65(509-524) peptides, binding of these peptides to intact I-Ag7 and assessed the effect of tolerance induction on diabetes development, by injecting young non-obese diabetic mice with high doses of peptide. RESULTS: T-cells from non-obese diabetic, but not other mice strains, spontaneously proliferate to the I-Ag7 86-101 and glutamic acid decarboxylase-65(509-524) peptides, but not control peptides. Both test peptides bind I-Ag7. Tolerance induction prolongs diabetes-free survival in non-obese diabetic mice when either the I-Ag7 86-101 or glutamic acid decarboxylase-65(509-524) peptide, but not control peptide, is used. CONCLUSION/INTERPRETATION: A peptide from the unique class II major histocompatibility complex, diabetes-susceptibility molecule, I-Ag7, presented by I-Ag7 is a target of T-cell responses in diabetes-prone nonobese diabetic mice and tolerance induction against the peptide offers appreciable protection against the development of diabetes.
A physical method for separating spermatozoa from epithelial cells in sexual assault evidence.
The analysis of genetic markers for the purpose of individualization of semen specimens is extremely important in cases of sexual abuse and assault. The serological analysis of sexual assault evidence can sometimes be complicated because stains are often composed of a mixture of spermatozoa, vaginal epithelial cells and white and red blood cells. A filtration method has been developed to cleanly separate spermatozoa from epithelial cells based upon differences in size and shape. Nylon mesh filters of the appropriate pore size can be used to separate the smaller oval shaped spermatozoal cells from the larger and flatter epithelial cells. The former pass freely through the membrane while the latter are retained on the filter. In this study, cell separation was demonstrated by (a) microscopic observation of stained cells, (b) amplified fragment length polymorphism analysis of DNA obtained from separated cells. The results of these analyses indicate that: (1) Approximately 70% of spermatozoa in the mixed cell sample will penetrate the 10 microns pore size filter, (2) Only about 1-2% of intact epithelial cells will do so, and (3) A small number of nuclei from spontaneously lysed epithelial cells will cross the filter. Experimental results using mixtures of spermatozoa and vaginal epithelial cells prepared in different ratios support the conclusion that the filtration process is an efficient and reliable method to separate spermatozoa from epithelial cells in casework specimens for subsequent DNA analysis.
Clinical performance of the new cardiac markers troponin T and CK-MB on the Elecsys 2010. A multicentre evaluation.
Elecsys assays for the cardiac markers Troponin T (cTnT) and CK-MB have been evaluated in an international multicenter study on the random access analyzer Elecsys 2010 to characterize their clinical performance and their comparability with respective established routine methods. In method comparison studies of Elecsys Troponin T (TnT) with Enzymun-Test TnT, good correlations (r > or = 0.95) and a high degree of correspondence (slopes in 4 laboratories between 0.95 and 1.05) were found. The method comparison studies of Elecsys CK-MB with various CK-MB routine methods lead to good correlations but some systematic deviation in the slopes due to varying standardization. In a reference population of 350 persons upper reference limits (97.5th percentile) of 0.03 milligrams/l for Elecsys TnT and 3.1 milligrams/l for Elecsys CK-MB were found. In cardiosensitivity studies the equivalent diagnostic information of the new Elecsys assays to routine methods was confirmed in the early diagnosis of acute myocardial infarction (AMI), the detection of minor myocardial damages in patients with unstable angina pectoris (UAP) and in time course data monitoring of AMI and bypass surgery patients. The superior sensitivity of cTnT versus CK-MB has been established in a screening situation where in 29 patients with cardiac diseases only cTnT, but not CK-MB, was found pathologically increased; this was due either to the larger diagnostic window of cTnT in AMI or to the more sensitive recognition of minor myocardial damage. In the same study, the cardiospecificity of Elecsys TnT was found to be at least 99.5%. This has also been demonstrated in an earlier study for Enzymun-Test TnT. Further cardiospecificity testing, e.g. in renal failure patients, showed results equivalent to those of Enzymun-Test TnT. An extended clinical study involving 294 patients with chest pain, of whom 58 had a final diagnosis of AMI, revealed highly comparable sensitivity and specificity for the Elecsys assays and routine methods. Thus, the already recommended clinical cut-off values of 0.1 milligrams/l for cTnT and 5 milligrams/l for CK-MB are also valid for the Elecsys assays. The slightly improved sensitivity of Elecsys TnT in the lower range even allows the recognition of pathological increase at cTnT concentrations below 0.1 milligrams/l in special situations with sufficient additional clinical information. Summarizing, provide the two cardiac markers on the Elecsys 2010 at least equivalent or even superior diagnostic information in various clinical situations of cardiac disease compared with routine methods. The short turn-around time and reliable performance qualify the Elecsys assays as new methods of choice for routine and emergency use.
Multiplexing of Y chromosome specific STRs and performance for mixed samples.
A combination of four Y-specific polymorphic STR loci was amplified simultaneously using fluorescently labeled primers. Multiplex conditions required optimization to eliminate constant bands and amplification products for female DNA. A series of experiments was carried out for mixtures of DNA from two males, and from male and female individuals for the Y-specific STRs and an autosomal locus. For the male/male mixtures amplified with the Y specific system, and amplified for an autosomal locus, the minor component in the mixture could only be identified up to a ratio of 1:10, 1:50 respectively. In male/female DNA mixtures the Y STR alleles could be identified for the highest ratio tested, 400 pg male in DNA in 800 ng female DNA which amounts to a ratio of 1:2000.
Molecular mimicry with MHC-derived peptides: does this underlie MHC association with autoimmune disease?
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Evaluation of a rapid, quantitative cardiac troponin I immunoassay.
We evaluated a rapid, quantitative immunoassay for the detection of cardiac troponin I. Coefficient of variation is between 1.29 and 13.63% for intra-assay and between 3.88 and 10.15% for inter-assay imprecision. Linearity is given up to 35 micrograms/l. Possible interfering substances (haemoglobin, bilirubin, triacylglycerol and rheuma factors) do not disturb the assay. The analyte is stable under normal storage conditions (+20 degrees C/48 h and +4 degrees C/l week) with decrease up to 30% after 3 months at -20 degrees C. Reference value for apparently healthy individuals is < 0.1 microgram/l. In plasma cardiac troponin I is measured up to 30% depressed compared to serum. Comparison with another cardiac troponin I assay (y = 0.92x + 2.42, r = 0.940) and cardiac troponin T is good with y = 6.61x - 1.94, r = 0.91 for the first generation cardiac troponin T assay and y = 5.59x - 0.68, r = 0.87 for the second generation cardiac troponin T assay. In summary, the evaluated assay is fast, easy to perform, and can be used not only in a specialized laboratory, but is also suitable for emergency laboratory or smaller laboratory units.
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.
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.
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.
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.
Molecular mimicry and the T-cell repertoire.
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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.
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.
Cardiac troponin T in patients with high creatinine concentration but normal creatine kinase activity in serum.
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Troponin T and troponin I after coronary artery bypass grafting: discordant results in patients with renal failure.
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