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A Manz

Publications and source records attributed to A Manz.

At least 19 recordsLinked to original sources
PubMed1998

Chemical amplification: continuous-flow PCR on a chip.

A micromachined chemical amplifier was successfully used to perform the polymerase chain reaction (PCR) in continuous flow at high speed. The device is analogous to an electronic amplifier and relies on the movement of sample through thermostated temperature zones on a glass microchip. Input and output of material (DNA) is continuous, and amplification is independent of input concentration. A 20-cycle PCR amplification of a 176-base pair fragment from the DNA gyrase gene of Neisseria gonorrhoeae was performed at various flow rates, resulting in total reaction times of 90 seconds to 18.7 minutes.

DNA Topoisomerases, Type II↗
PubMed1998

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗
PubMed1998

Immune cell functions in industrial workers after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: dissociation of antigen-specific T-cell responses in cultures of diluted whole blood and of isolated peripheral blood mononuclear cells.

A comparative analysis was performed of the phenotype and function of peripheral blood leukocytes of two age-matched cohorts of industrial workers in chemical plants, one of which was exposed occupationally to high concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Median actual TCDD burdens were 116 ng/kg and 4 ng/kg, respectively. The phenotype analysis of peripheral blood mononuclear cells (PBMC) revealed no significant differences in the proportions of CD3, CD4, or CD8+ T lymphocytes, of CD16+ natural killer cells, and of CD19+ B lymphocytes. However, in PBMC of the TCDD-exposed workers; the proportion of CD8+ memory T cells (CD45R0+) was significantly higher, and that of lymphocytes with naive phenotype (CD45RA+) was significantly lower than in PBMC of the control group. Polyclonal and antigen-specific T-cell activation was assessed in parallel in isolated PBMC as well as in diluted whole blood cultures. In both culture systems the polyclonally stimulated cytokine release did not differ significantly between the two cohorts; however, we found a significantly reduced interferon gamma release in diluted whole blood cultures but not in isolated PBMC cultures of the TCDD-exposed cohort when we performed an antigen-specific T-cell stimulation with tetanus-toxoid. Therefore, we propose that exposure of individuals to high doses of TCDD can partially impair in the "blood milieu" those T-cell/monocyte interactions that are essential for antigen-specific T-cell responses, whereas isolated PBMC of the same donors appear functionally less affected.

Adult↗
PubMed1997

Developments in technology and applications of microsystems.

In the past year, microchips as applied to miniaturised total analysis systems, or microTAS, have benefited from technological improvements in their fabrication and been applied to analysis in many different biological areas. From a technological perspective, salient work includes fast, cheap and easy micromachining in polymers and integrated optical detection. From the bioapplications perspective, advances in DNA and protein separations, cell manipulations, immunoassays and polymerase chain reaction using on-chip electrophoretic separation stand out.

Chemistry Techniques, Analytical↗
PubMed1997

Elimination of beta-hexachlorocyclohexane in occupationally exposed persons.

The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of beta-HCH. The data support the assumption of first-order kinetics.

Adipose Tissue↗
PubMed1997

Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors.

A prototype miniaturized Total Chemical Analysis System (muTAS) has been developed and applied to on-line monitoring of glucose and lactate in the core blood of anaesthetized dogs. The system consists of a highly efficient microdialysis sampling interface sited in a small-scale extracorporeal shunt circuit ('MiniShunt'), a silicon machined microflow manifold and integrated biosensor array for glucose and lactate detection with associated computer software for analytical process control. During in-vivo testing the device allowed real-time on-screen monitoring of glucose and lactate with system response times of less than 5 min, made possible by the small dead volume of the microflow system. On-line glucose and lactate measurements were made in the basal state as well as during intravenous infusion of glucose or lactate. The prototype muTAS is currently suitable for trend monitoring but refinements are necessary before application of the system for determination of individual lactate values.

Animals↗
PubMed1996

Micellar electrokinetic chromatography separations and analyses of biological samples on a cyclic planar microstructure.

Micellar electrokinetic capillary chromatography (MECC) separations and analyses of biological samples on a planar glass microchip capillary electrophoresis device with laser-induced fluorescence solute detection are discussed. A cyclic channel system which permits dead volume free repeated column switching and thus the use of various channel lengths together with a relatively low applied separation voltage is described. It features an unbiased, dead volume free electrokinetic sample inlet system of approximately 12 pL. Because of the small cross section and favorable heat dissipation in glass microstructures, MECC separations with an electric field strength of up to 2000 V/cm achieving efficiencies of submicrometer plate heights can be performed. After a separation length of 2 cm, six fluorescein isothiocyanate labeled amino acids are shown to be separable within a few seconds and with an imprecision for peak areas (or heights) and detection times of < 2% and < 0.5%, respectively. Without application of electrokinetic solute stacking, the detection limit of fluorescein isothiocyanate labeled arginine is 3.3 nM, corresponding to approximately 40 zmol injected. Furthermore, the feasibility of directly applying human urine and serum samples onto the uncoated channel system is demonstrated and first data of the successful performance of a chip-based MECC immunoassay for serum theophylline are presented. Compared to MECC in conventional fused-silica capillaries, MECC analyses on microchips can be performed 1-2 orders of magnitude faster, with higher efficiency and at no expense of accuracy and precision. Furthermore, versatility is shown to be much increased with the use of a cyclic rather than a single-path channel system. The MECC separation efficiency of fluorescein isothiocyanate labeled amino acids is shown to be comparable to that obtained by gel electrophoresis performed in the same chip layout.

Amino Acids↗
PubMed1996

Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.

In an occupational cohort study, the relation between exposure to phenoxy herbicides, and contaminants (dioxins and furans) and cancer mortality was investigated. A total of 2,479 workers from four plants in Germany were included, with a mortality follow-up until the end of 1989 (for one cohort, until the end of 1992). A total of 484 deaths were recorded yielding a standardized mortality ratio (SMR) of 101 (95 percent confidence interval [CI] = 92-111) for total mortality, and an SMR of 119 (CI = 100-141) for all malignant diseases. A variety of herbicides was produced, including those which are known to have been contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). High dioxin and furan exposure (in particular, exposure to TCDD, but also to higher chlorinated dioxins) had occurred in two of the four plants as shown by blood-fat measurements in a sample of workers. Mortality from all neoplasms increased with latency and was highest in the largest plant where the highest TCDD blood levels were recorded. An increased mortality in the total cohort from respiratory cancer (SMR = 154, CI = 115-202), cancer of the buccal cavity and pharynx (SMR = 295, CI = 135-560), and non-Hodgkin's lymphoma (SMR = 326, CI = 119-710) was observed. Our findings are consistent with results from other cohorts which showed an increased overall cancer mortality and mortality of respiratory cancer after long-term exposure to these phenoxy herbicides and dioxins.

Adipose Tissue↗
PubMed1996

Elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in occupationally exposed persons.

The elimination of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was investigated in a group of n = 43 exposed workers with 2 blood measurements and n = 5 workers with 3 measurements. Under the assumption of a one-compartment, first-order kinetic model the median half-life for 2,3,7,8-TCDD was 7.2 yr, while for the other dioxins the estimates were between 3.7 yr for 1,2,3,4,6,7,8-HpCDD (hepta-chlorinated) and 15.7 yr for 1,2,3,7,8-PCDD (penta-chlorinated). For the furans median half-lives between 3.0 yr for 1,2,3,4,6,7,8-HpCDF and 19.6 yr for 2,3,4,7,8-PCDF were observed. There was no indication for a deviation from a first-order kinetic. Increasing age and percent body fat were associated with increasing half-life for most of the congeners. Smokers in general had a faster decay than non- and ex-smokers. In summary, the higher chlorinated PCDD/F like TCDD appear to be highly persistent in humans with half-lives ranging between 4 and 12 yr.

Adipose Tissue↗
PubMed1995

Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany.

The relation between mortality (all cause; cancer; cardiovascular diseases (International Classification of Diseases, Ninth Revision (ICD-9), codes 390-459); ischemic heart diseases (ICD-9 codes 410-414)) and exposure to polychlorinated dibenzo-p-dioxins and -furans (PCDD/F) was investigated in a retrospective cohort study. The cohort consisted of 1,189 male workers in a chemical plant in Hamburg, Federal Republic of Germany, who had produced phenoxy herbicides, chlorophenols, and other herbicides and insecticides known to be contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and other, higher chlorinated dioxins and furans. The authors reported previously on cancer mortality in this cohort for the follow-up period 1952-1989. The current study covers the years 1952-1992 and investigates the relation of PCDD/F exposure to mortality using a quantitative estimate of PCDD/F exposure for the whole cohort derived from blood and adipose tissue levels measured in a subgroup (n = 190). Quintiles and deciles of these estimates served as dose parameters in the estimation of relative risks (RRs), using year-of-birth stratified Cox regression. An unexposed cohort of gas workers served as an external reference group. The total mortality was elevated in all dose groups. The highest relative risk was observed for the highest 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decile (RR = 2.43, 95% confidence interval (CI) 1.80 to 3.29). Cancer mortality and mortality due to ischemic heart diseases showed a dose-dependent relation with TCDD and all PCDD/F combined. The highest relative risks for cancer (RR = 3.30, 95% CI 2.05 to 5.31) and ischemic heart diseases (RR = 2.48, 95% CI 1.32 to 4.66) were observed in the highest PCDD/F exposure group. The pattern of effects and tests for trend were similar when the lowest exposure group within the chemical worker cohort served as the reference, but the relative risks were smaller and the confidence intervals were larger. Potential confounding exposures complicate the interpretation of the internal comparison. These findings indicate a strong dose-dependent relation between mortality due to cancer or ischemic heart diseases and exposure to polychlorinated dioxins and furans.

Causality↗
PubMed1993

When is a cluster?

Explore the source record for details and available documents.

Epidemiologic Methods↗
PubMed1993

An integrated silicon thermophile as biosensor for the thermal monitoring of glucose, urea and penicillin.

A new kind of calorimetric biosensor for the measurement of the heat (molar enthalpy change) of enzymatic reactions is presented. The device operates according to the Seebeck effect, the same principle on which thermocouples are based. The thermopile used in this work consists of an array of p-type silicon/aluminium strips integrated on a thin silicon membrane (5 microns). Its sensitivity is about 1 V output voltage per watt of heating power, corresponding to a temperature resolution in the order of 10(-5) K and a heating power resolution of some tenths of a mu W in the flow system used. Furthermore, this performance is obtained without any control of external temperature because of the high common-mode thermal noise rejection ratio of the thermopile. The universal technique of calorimetry combined with the specificity of biochemical reactions makes this biosensor very versatile, with a broad range of possible applications. Glucose oxidase together with catalase for the determination of glucose, urease and penicillinase for the monitoring of urea and penicillin G, respectively, were immobilized directly onto the back side of the thermopile. The sensor was operated in conjunction with flow injection analysis which, in addition to its traditional advantages, allows preconditioning of the samples. Thus, artefacts due to mixing effects were suppressed and interference caused by differences in ionic strength between sample and carrier was strongly decreased. Detection limits between 1 and 2 mM were reported in the flow injection conditions described.

Biosensing Techniques↗
PubMed1992

Cancer of the stomach and the colon-rectum among workers in a coke gas plant.

Four thousand nine hundred and eight male workers of the Hamburg gas plant, employed for 10 or more years during the period from January 1, 1900 to December 31, 1989, have been traced for cancer mortality. Based on their jobs, they were grouped into three subcohorts: gas furnace workers, workers in other parts of the plant, and white-collar workers. Despite the general "healthy worker effect," gas furnace workers showed a significant incidence of cancer of all sites (standardized mortality ratio [SMR] = 186), particularly cancers of the lung (SMR = 288), stomach (SMR = 177), and the colon-rectum (SMR = 184). In comparison to the death rates of white-collar workers, the manual workers in other parts of the plant also showed an excess of cancer mortality for cancer of these sites. The reason for this excess in cancer mortality seems to be due to the working conditions. The results contribute to the current evidence that exposure to coal carbonization fumes causes not only lung cancer, but also cancers of the stomach and colon-rectum.

Adult↗
PubMed1992

Flow injection analysis and in-line biosensors for bioprocess control: a comparison.

Miniaturization will unify the different approaches chosen for the application of biosensors in bioprocess control. The most versatile system, which in our opinion is flow injection analysis will be the method of choice for the introduction of biosensors in bioprocess control. A lot of experience will be gained for the future development of miniaturized total chemical analysis systems.

Biosensing Techniques↗
PubMed1991

Cancer mortality among workers in chemical plant contaminated with dioxin.

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD) can arise as a contaminant in the production of herbicides. It causes chloracne in those exposed to it but its human carcinogenicity has been a matter of dispute. We report here a mortality follow-up of 1583 workers (1184 men, 399 women) employed in a chemical plant in Germany that produced herbicides, including processes contaminated with TCDD. Production of TCDD was reduced from 1954 after an outbreak of chloracne. Vital status up to 1989 was determined for 97.1% of workers hired between 1952 and 1984, and 367 deaths (313 men, 54 women) were recorded. A malignant neoplasm was the underlying cause of death in 93 men and 20 women. Standardised mortality ratios (SMR) were calculated with, as references, national mortality statistics for West Germany and deaths in a cohort of male gas workers; for total cancer mortality they were 1.24 (95% confidence interval 1.00-1.52) and 1.39 (1.10-1.75), respectively, among men. Cancer mortality was increased among men with 20 or more years of employment (SMR = 1.87 [Germany] and 1.82 [gas workers]) and among men who began employment before 1955 (SMR = 1.61 and 1.87). The group with suspected highest exposure to TCDD had SMRs of 1.42 and 1.78. Only 7% of cohort women worked in the high exposure locations in the plant, compared with 39.6% of men, and no increased risk of cancer mortality was observed among women; but breast cancer mortality was raised (SRM = 2.15). These results, together with a US occupational study and a German investigation of accidental exposure, support the hypothesis that TCDD is a human carcinogen.

Cause of Death↗
PubMed1991

[The usefulness of death certificates in epidemiological studies].

An analysis of a total of 189 deaths recorded between 1953 and 1990 from two companies in Hamburg was performed to examine the question whether and if so to what extent differences existed between the causes of death (primary disease) stated in the death certificates on the one hand, and the diagnoses based on subsequent medical (clinical and pathologico-anatomical) reports, on the other. Postmortems were conducted in 94 cases; the diagnoses resulting therefrom had also been taken into consideration in 58 of the pertaining death certificates. Considerable differences were seen for the remaining 36 postmortems where only clinical diagnoses were recorded in the death certificates. In 10 cases (= 27.8%) the statements made in the death certificates did not agree with the PM diagnoses. The overall rate of deviations was 12.7% the figures for the individual fatal diseases varied, the greatest difference occurring with diseases of the heart and with chronic bronchitis and the least difference with acute apoplexy, accidents, suicides and malignant tumours. It is noted that death certificates and hence also the official statistics derived therefrom are but an inaccurate reflection of the actual distribution of causes of death in case of unicausal evaluations. The quota of diagnoses based on PM and actually taken into consideration, is an important factor in this regard. However, the data supplied by the death certificates are reasonably useful for epidemiological studies to estimate the risks involved in certain diseases.

Autopsy↗