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Biomedical subjects

Michael Klein

Publications and source records attributed to Michael Klein.

At least 19 recordsLinked to original sources
PubMed2007

Accumulation of immune cells and high expression of chemokines/chemokine receptors in the upstream shoulder of atherosclerotic carotid plaques.

The presence of immune cells is important for plaque destabilization. Disturbed flow conditions were shown to enhance the recruitment of circulating immune cells. Thus, we analyzed in 54 atherosclerotic carotid plaques the frequency of different immune cells, HLA-DR, chemokines, and chemokine receptors, comparing the upstream with the downstream plaque shoulder. The presence of neovascularization and intraplaque hemorrhages was investigated by CD34 immunostaining and Mallory's iron stain. Immunohistochemical analyses were performed to detect smooth muscle cells (SMC: actin), macrophages (CD68), T cells (CD3), dendritic cells (DC: fascin), mature DC (CD83), and the expression of HLA-DR, chemokine receptors (CCR-2, CCR-6), and chemokines (MCP-1, MIP-3alpha). Significantly more SMC were detected downstream than upstream (p<0.001). In contrast, significantly more macrophages (p=0.01), DC (p=0.03), mature DC (p=0.007), and a higher expression of HLA-DR (p=0.004), CCR-2 (p=0.002), CCR-6 (p<0.001), MCP-1 (p=0.04), and MIP-3alpha (p=NS) were observed upstream than downstream. Immune cells were strongly associated with neovascularization. The abundance of SMC downstream provides an explanation for distal plaque growth. Enhanced recruitment of immune cells through neovessels into the upstream shoulder might be contributing to plaque destabilization.

Aged↗
PubMed2006

Decrease in circulating myeloid dendritic cell precursors in coronary artery disease.

OBJECTIVES: We analyzed the frequency of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) precursors in blood of patients with coronary artery disease (CAD) and in atherosclerotic carotid plaques of patients with cerebrovascular disease (CVD). BACKGROUND: Circulating DC precursors are reduced in several autoimmune diseases. Atherosclerosis has features of an autoimmune disease, such as the presence of autoantibodies or autoreactive T cells. Tissue-resident DCs were previously described in atheromata, and it is assumed that they are important for the activation of T cells against autoantigens there. METHODS: Circulating mDC and pDC precursors were flow cytometrically detected in healthy controls (n = 19), CAD patients with stable (n = 20) and unstable angina pectoris (n = 19), and acute myocardial infarction (n = 17). In human carotid plaques (n = 65), mDC and pDC precursors were identified immunohistochemically. RESULTS: Circulating mDC precursors were significantly reduced in patients with stable angina pectoris (0.19%, p = 0.04), unstable angina pectoris (0.16%, p = 0.004), and acute myocardial infarction (0.08%, p < 0.001) compared with control patients (0.22% of peripheral blood mononuclear cells). In contrast, pDC numbers were not significantly altered. Circulating mDC precursors inversely correlated with high-sensitivity C-reactive protein (r = -0.38, p = 0.001) or interleukin-6 (r = -0.42, p < 0.001). In contrast to pDC, significantly more mDC precursors were observed in vulnerable carotid plaques (24, 0.25 mm2; n = 31; p = 0.003) than in stable ones (6.4, 0.25 mm2; n = 34). CONCLUSIONS: Similar to autoimmune diseases, circulating mDC precursors were significantly reduced in patients with CAD. The emergence of mDC precursors in vulnerable plaques suggests their recruitment into atheromata as a possible reason for their decrease in blood. In contrast, no significant association of circulating pDC precursors with atherosclerosis was observed.

Aged↗
PubMed2006

Atypical extraspinal musculoskeletal tuberculosis in immunocompetent patients, a review. Part I: atypical osteoarticular tuberculosis and tuberculous osteomyelitis.

With the resurgence of pulmonary tuberculosis and musculoskeletal tuberculosis in North America and Europe over the last 20 years, the typical pattern of extraspinal musculoskeletal tuberculosis has been changing; presentation of the disease often mimics that of neoplasia. However, certain radiographic features may offer some clues to the more benign nature of the process and its inflammatory and infectious nature. Although the diagnosis of extraspinal musculoskeletal tuberculosis depends largely on clinical context, it is the radiologist's role to guide the imaging workup to initiate the specific treatment as early as possible. As in classic extraspinal tuberculosis, delayed diagnosis may lead to deformity of the involved joint and permanent disability. This review considers atypical osteoarticular tuberculosis and tuberculous osteomyelitis. We discuss examples of these atypical presentations. All patients were permanent residents in Europe and North America, and all were immunocompetent.

Humans↗
PubMed2005

DNA index determination with Automated Cellular Imaging System (ACIS) in Barrett's esophagus: comparison with CAS 200.

BACKGROUND: For solid tumors, image cytometry has been shown to be more sensitive for diagnosing DNA content abnormalities (aneuploidy) than flow cytometry. Image cytometry has often been performed using the semi-automated CAS 200 system. Recently, an Automated Cellular Imaging System (ACIS) was introduced to determine DNA content (DNA index), but it has not been validated. METHODS: Using the CAS 200 system and ACIS, we compared the DNA index (DI) obtained from the same archived formalin-fixed and paraffin embedded tissue samples from Barrett's esophagus related lesions, including samples with specialized intestinal metaplasia without dysplasia, low-grade dysplasia, high-grade dysplasia and adenocarcinoma. RESULTS: Although there was a very good correlation between the DI values determined by ACIS and CAS 200, the former was 25% more sensitive in detecting aneuploidy. ACIS yielded a mean DI value 18% higher than that obtained by CAS 200 (p < 0.001; paired t test). In addition, the average time required to perform a DNA ploidy analysis was shorter with the ACIS (30-40 min) than with the CAS 200 (40-70 min). Results obtained by ACIS gave excellent inter-and intra-observer variability (coefficient of correlation > 0.9 for both, p < 0.0001). CONCLUSION: Compared with the CAS 200, the ACIS is a more sensitive and less time consuming technique for determining DNA ploidy. Results obtained by ACIS are also highly reproducible.

Journal Article↗
PubMed2005

Connective tissue growth factor is overexpressed in complicated atherosclerotic plaques and induces mononuclear cell chemotaxis in vitro.

OBJECTIVE: Atherosclerotic blood vessels overexpress connective tissue growth factor (CTGF) mRNA, but the role of CTGF in atherosclerosis remains controversial. To assess the hypothesis that CTGF is involved in atherosclerotic plaque progression, we investigated CTGF protein expression and distribution in the different types of plaque morphology. METHODS AND RESULTS: Serial cross-sections of 45 human carotid plaques were immunohistochemically analyzed for the presence of CTGF protein, neovascularization (von Willebrand factor), macrophages (CD68), and T cells (CD3). The lesions were categorized according to American Heart Association (AHA) classification as fibrous (type IV and V) or complicated plaques (type VI). The levels of CTGF were significantly higher in complicated compared with fibrous plaques (P=0.002). CTGF accumulated particularly in the rupture-prone plaque shoulder and in the areas of neovascularization or infiltration with inflammatory cells. Macrophage-like cells stained positive for CTGF protein in plaques. Subsequent in vitro studies showed that although monocyte-derived macrophages do not produce CTGF on stimulation with transforming growth factor-beta, lipopolysaccharide, or thrombin, they take it up from culture medium. Furthermore, CTGF induces mononuclear cell chemotaxis in a dose-dependent manner. CONCLUSIONS: CTGF protein is significantly increased in complicated compared with fibrous plaques and may enhance monocyte migration into atherosclerotic lesions, thus contributing to atherogenesis.

Aged↗
PubMed2005

Prediction of pesticide volatilization with PELMO 3.31.

In the current EU risk assessment for pesticide registration, the European Community requires prediction of the concentration of each pesticide in air. A number of mathematical models are used to assess the fate of pesticides in groundwater, surface water and soil. PELMO 3.20 calculates the volatilization fluxes from bare soil and was improved in the new version PELMO 3.31 to include the effect of temperature and sorption in dry soil. The objective of this study was to evaluate the new version of PELMO 3.31 in predicting the pesticide volatilization under field conditions. Procymidone, malathion, and ethoprophos were the test compounds in two different seasons (autumn and winter). Comparing simulation results obtained with PELMO 3.31, after calibration, with the previous version PELMO 3.20 shows that the estimated volatilization results seems improved for malathion, similar or slightly overestimating in the warmer season for ethoprophos, and similar or slightly underestimating in the colder season for procymidone. The new release of PELMO allows a more accurate estimation of pesticides volatilization from soil as function of meteorological factors, especially for medium or low volatility pesticides. Some difficulties remain, such as the determination of the active air layer and the sorption increment with the soil drying.

Air Pollutants↗
PubMed2005

Functional marker genes for identification of sulfate-reducing prokaryotes.

Sulfate-reducing prokaryotes (SRPs) exploit sulfate as an electron acceptor for anaerobic respiration and exclusively catalyze this essential step of the world's sulfur cycle. Because SRPs are found in many prokaryotic phyla and are often closely related to non-SRPs, 16S rRNA gene-based analyses are inadequate to identify novel lineages of this guild in a cultivation-independent manner. This problem can be solved by comparative sequence analysis of environmentally retrieved gene fragments of the dissimilatory (bi)sulfite (dsrAB) and adenosine-5'-phosphosulfate reductases (apsA), which encode key enzymes of the SRP energy metabolism. This chapter provides detailed protocols for the application of these functional marker molecules for SRP diversity surveys in the environment. Data from the analysis of dsrAB sequence diversity in water samples from the Mariager Fjord in northeast Denmark are presented to illustrate the different steps of the protocols. Furthermore, this chapter describes a novel gel retardation-based technique, suitable for fingerprinting of the approximately 1.9-kb-large dsrAB polymerase chain reaction amplification products, which efficiently increases the chance of retrieving rare and novel dsrAB sequence types from environmental samples.

Bacteria, Anaerobic↗
PubMed2005

Lateral gene transfer of dissimilatory (bi)sulfite reductase revisited.

In contrast to previous findings, we demonstrate that the dissimilatory (bi)sulfite reductase genes (dsrAB) of Desulfobacula toluolica were vertically inherited. Furthermore, Desulfobacterium anilini and strain mXyS1 were identified, by dsrAB sequencing of 17 reference strains, as members of the donor lineage for those gram-positive Desulfotomaculum species which laterally acquired dsrAB.

Bacteria, Anaerobic↗
PubMed2005

Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration.

The liver has a large capacity for regeneration after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSCs) to participate in liver regeneration. Here we report on three patients subjected to intraportal administration of autologous CD133(+) BMSCs subsequent to portal venous embolization of right liver segments, used to expand left lateral hepatic segments as FLRV. Computerized tomography scan volumetry revealed 2.5-fold increased mean proliferation rates of left lateral segments compared with a group of three consecutive patients treated without application of BMSCs. This early experience with portovenous application of CD133(+) BMSCs could suggest that this novel therapeutic approach bears the potential of enhancing and accelerating hepatic regeneration in a clinical setting.

AC133 Antigen↗
PubMed2004

Pesticide volatilization from plants: improvement of the PEC model PELMO based on a boundary-layer concept.

Calculation of pesticide volatilization from plants as an integral component of pesticide fate models is of utmost importance, especially as part of PEC (predicted environmental concentrations) models used in the registration procedures for pesticides. A mechanistic approach using a laminar air-boundary layer concept to predict volatilization from plant surfaces was compared to data obtained in a wind-tunnel study after simultaneous application of parathion-methyl, fenpropimorph, and quinoxyfen to winter wheat. Parathion-methyl was shown to have the highest volatilization during the wind-tunnel study of 10 days (29.2%). Volatilization of quinoxyfen was about 15.0%, revealing a higher volatilization tendency than fenpropimorph (6.0%), which is attributed to enhanced penetration of fenpropimorph counteracting volatilization. Predictions of the boundary-layer approach were markedly influenced by the selected values for the equivalent thickness of the boundary layer and rate coefficients, thus indicating that future improvements of the approach will require a deeper understanding of the kinetics of the underlying processes, e.g. phototransformation and penetration. The boundary-layer volatilization module was included in the European registration model PELMO, enabling simultaneous calculation of volatilization from plants and soil. Application of PELMO to experimental findings were the first comprehensive PEC model calculations to imply the relevant processes affecting the postapplication fate of pesticides.

Carbon Radioisotopes↗
PubMed2004

Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus.

In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment can lead to columnar-lined esophagus (CLE) including metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). This study describes the morphology and phenotypic features of CLE and EAC in the rat model and compares them with the corresponding lesions in human Barrett's esophagus (BE). Swiss roll preparations of esophagi of EGDA rats and biopsies from human BE containing specialized intestinal metaplasia (SIM) and EAC were examined. The esophagi of EGDA rats showed esophagitis, CLE, islands of multilayered epithelium (MLE), dysplasia and EAC. The CLE had features of specialized intestinal metaplasia. MLE frequently occurred at the neo-squamocolumnar junction and occasionally in the mid-esophagus in isolated foci. Scattered mucinous cells in esophageal squamous epithelium were also found. The CLE and MLE in EGDA rats resembled the lesions described in human BE in morphology, mucin features and expression of differentiation markers (CK7, CK20, Das-1, villin, and pS2/TFF1). Invasive EAC in EGDA rat is of well-differentiated mucinous type, which is in contrast to the variably differentiated glandular type of adenocarcinoma in human BE. p53, c-myc, and cyclooxygenase 2 are expressed in both the rat and human SIM and EAC. These studies indicate that, not withstanding small differences, SIM and EAC induced in EGDA rats are similar to the corresponding lesions in human BE. EGDA rats may serve as a useful model to study the pathogenesis, molecular biology, and chemopreventive interventions of human BE and EAC.

Adenocarcinoma↗
PubMed2004

DNA abnormalities as marker of risk for progression of Barrett's esophagus to adenocarcinoma: image cytometric DNA analysis in formalin-fixed tissues.

OBJECTIVES: To examine DNA content abnormalities in patients with Barrett's esophagus (BE) who progress to esophageal adenocarcinoma, using image cytometric DNA analysis (ICDA) of formalin-fixed tissues. METHODS: Studies were performed on archived biopsies of BE patients' undergoing endoscopic surveillance before developing adenocarcinoma. A comparison group consisted of BE patients' free of cancer during a follow-up period of over 9 yr. Tissue sections were analyzed for the degree of dysplasia and for DNA content abnormalities, using image cytometry. Additional patients were also analyzed in a cross-sectional study of 56 BE cases with and without dysplasia, including 12 cases of adenocarcinoma. RESULTS: Five patients developed adenocarcinoma during follow-up and earlier biopsies obtained before cancer diagnosis showed specialized intestinal metaplasia (SIM) followed by low-grade dysplasia (LGD) in one, SIM followed by high-grade dysplasia (HGD) in one, LGD in two, and HGD in one case. All five showed some DNA abnormality at baseline or in interval biopsies. In the comparison group, five of seven patients showed normal diploid DNA at baseline and on follow-up biopsies. One patient initially had diploid DNA, but developed aneuploidy 11 yr later. Another case initially had aneuploidy, but was diploid on follow-up. Overall, DNA abnormalities were found in 13% of cases with SIM without dysplasia, 60% with LGD, 73% with HGD, and 100% with adenocarcinoma. CONCLUSIONS: (i) Image cytometric DNA analysis is a useful method to examine DNA abnormalities in formalin-fixed tissues and may be more sensitive in predicting progression to adenocarcinoma than HGD. (ii) Histological dysplasia of any grade and DNA abnormalities, help identify BE patients at high risk for adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Tetrahydroxy 10-membered cyclic enediynes.

The preparation of cyclic 10-membered tetrahydroxy enediynes is reported. The synthesis starts from tartaric acid and allows the control of the relative stereochemistry. Acetal protection of the 2,3-hydroxy groups stabilizes the enediyne during synthesis. Removal of the cyclic protecting group with EtSH/TFA transforms the stable compounds into reactive enediynes, and the rate constants of their cyclization were determined in benzene and water. The cytoxicity of the activated compounds was assayed against tumor cells in vitro, but the growth inhibitory effect was weak compared to cisplatin.

Cell Line, Tumor↗
PubMed2003

Permeation of cytotoxic formulations through swatches from selected medical gloves.

The permeability of selected medical glove materials to various cytotoxic agents is described. Fifteen cytotoxic agents were prepared at the highest concentrations normally encountered by hospital personnel. Four single-layer and two double-layer glove systems made of two materials--latex and neoprene--were exposed to the drugs for 30, 60, 90, 120, 150, and 180 minutes. Circular sections of the glove material were cut from the cuff and evaluated without any pretreatment. Permeability tests were conducted in an apparatus consisting of a donor chamber containing the cytotoxic solution and a collection chamber filled with water (the acceptor medium). The two sections were separated by the glove material. Permeating portions, collected in water as the acceptor medium, were analyzed by either ultraviolet-visible light spectrophotometry or high-performance liquid chromatography (HPLC). Permeation rates were calculated on the basis of the concentration of the cytotoxic agent in the acceptor medium. Spectrophotometric measurements were taken every 30 minutes, and HPLC analysis was performed at the end of the three-hour period. Average permeation rates for 14 drugs were low (< 0.2 nmol/[min.cm2]) or no permeation was detected in all glove materials. All glove materials tested were impermeable to most of the cytotoxic agents over a period of three hours. Carmustine was the only agent that substantially permeated single-layer latex glove materials. Permeation of most tested cytotoxic formulations was low through swatches of material from various medical gloves.

Carcinogens↗
PubMed2003

Exercise in pregnancy and the postpartum period.

OBJECTIVE: To design Canadian guidelines advising obstetric care providers of the maternal, fetal, and neonatal implications of aerobic and strength-conditioning exercises in pregnancy. OUTCOMES: Knowledge of the impact of exercise on maternal, fetal, and neonatal morbidity, and of the maternal measures of fitness. EVIDENCE: MEDLINE search from 1966 to 2002 for English-language articles related to studies of maternal aerobic and strength conditioning in a previously sedentary population, maternal aerobic and strength conditioning in a previously active population, impact of aerobic and strength conditioning on early and late pregnancy outcomes, and impact of aerobic and strength conditioning on neonatal outcomes, as well as for review articles and meta-analyses related to exercise in pregnancy. VALUES: The evidence collected was reviewed by the Society of Obstetricians and Gynaecologists of Canada (SOGC Clinical Practice Obstetrics Committee) with representation from the Canadian Society for Exercise Physiology, and quantified using the evaluation of evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. All women without contraindications should be encouraged to participate in aerobic and strength-conditioning exercises as part of a healthy lifestyle during their pregnancy. (II-1,2B) 2. Reasonable goals of aerobic conditioning in pregnancy should be to maintain a good fitness level throughout pregnancy without trying to reach peak fitness or train for an athletic competition. (II-1,2C) 3. Women should choose activities that will minimize the risk of loss of balance and fetal trauma. (III-C) 4. Women should be advised that adverse pregnancy or neonatal outcomes are not increased for exercising women. (II-1,2B) 5. Initiation of pelvic floor exercises in the immediate postpartum period may reduce the risk of future urinary incontinence. (II-1C) 6. Women should be advised that moderate exercise during lactation does not affect the quantity or composition of breast milk or impact infant growth. (I-A) VALIDATION: This guideline has been approved by the SOGC Clinical Practice Obstetrics Committee, the Executive and Council of SOGC, and the Board of Directors of the Canadian Society for Exercise Physiology. SPONSORS: This guideline has been jointly sponsored by the Society of Obstetricians and Gynaecologists of Canada and the Canadian Society for Exercise Physiology.

Adult↗
PubMed2003

Recurrent syncope in a young patient with long QT syndrome: possible relationship of atrioventricular nodal re-entrant tachycardia with neurally mediated spells?

This is a case of a 15-year-old woman with long QT syndrome (LQTS) and a history of 14 events of syncope, demonstrating that the underlying mechanism for any symptomatic episode is not necessarily based on torsades de pointes. The need for careful distinction between true ventricular tachyarrhythmia and other forms of supraventricular tachycardia in the LQTS is the subject of the article. To the knowledge of the authors, this is the first reported case of an association of LQTS with AV nodal re-entrant tachycardia.

Adolescent↗