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Biomedical subjects

J Heinrich

Publications and source records attributed to J Heinrich.

At least 19 recordsLinked to original sources
PubMed1996

Hemostatic variables in the prediction of coronary risk: results of the 8 year follow-up of healthy men in the Münster Heart Study (PROCAM). Prospective Cardiovascular Münster Study.

Myocardial infarction is usually due to the acute formation of an occlusive thrombus within the coronary arteries, in most cases against a background of pre-existing coronary atherosclerosis. Both of these factors may be promoted by a procoagulant state of the hemostatic system. Plasma fibrinogen, factor VIIc, blood pressure, and lipid parameters were measured in 2,781 healthy men aged 40-65 in the Münster Heart Study (formerly known as the PROCAM Study). After 8 years of follow-up 130 coronary events (15 sudden cardiac deaths, 22 fatal myocardial infarctions, and 93 nonfatal myocardial infarctions) were observed. Plasma fibrinogen concentration and factor VIIc activity were significantly greater among men who suffered a coronary event. The mean plasma fibrinogen level of the event group exceeded that of the non-event group by 0.32 g/l [2.59 +/- 0.58 vs. 2.91 +/- 0.58 (mean +/- SD) respectively, P < 0.001]. The incidence of coronary events among men within the upper tertile of fibrinogen concentration was three times higher than among men within the lower tertile. Plasma factor VIIc activity was 112.4 +/- 20.1% in the event group and 108.7 +/- 21.4% in the non-event group (P < 0.05). Among men in the upper tertile of factor VIIc activity, the incidence of coronary events was 1.6 times that of men in the lower tertile. When fibrinogen and low density lipoprotein (LDL) concentration were considered together, there was a graded and dramatic eightfold increase in 8 year risk from 17 per 1,000 of population among men with both fibrinogen and LDL cholesterol in the lower tertiles to 130 per 1,000 in men with both of these parameters in the upper tertile. In men with LDL cholesterol in the lowest tertile, increasing fibrinogen levels did not increase the risk of a coronary event. The coagulation variables, fibrinogen concentration, and factor VIIc activity thus markedly improve our ability to predict coronary risk.

Adult↗
PubMed1995

Precursor of C4 antisense RNA of bacteriophages P1 and P7 is a substrate for RNase P of Escherichia coli.

The C4 repressor of the temperate bacteriophages P1 and P7 inhibits antirepressor (Ant) synthesis and is essential for establishment and maintenance of lysogeny. C4 is an antisense RNA acting on a target, Ant mRNA, which is transcribed from the same promoter. The antisense-target RNA interaction requires processing of C4 RNA from a precursor RNA. Here we show that 5' maturation of C4 RNA in vivo depends on RNase P. In vitro, Escherichia coli RNase P and its catalytic RNA subunit (M1 RNA) can generate the mature 5' end of C4 RNA from P1 by a single endonucleolytic cut, whereas RNase P from the E. coli rnpA49 mutant, carrying a missense mutation in the RNase P protein subunit, is defective in the 5' maturation of C4 RNA. Primer extension analysis of RNA transcribed in vivo from a plasmid carrying the P1 c4 gene revealed that 5'-mature C4 RNA was the predominant species in rnpA+ bacteria, whereas virtually no mature C4 RNA was found in the temperature-sensitive rnpA49 strain at the restrictive temperature. Instead, C4 RNA molecules carrying up to five extra nucleotides beyond the 5' end accumulated. The same phenotype was observed in rnpA+ bacteria which harbored a plasmid carrying a P7 c4 mutant gene with a single C-->G base substitution in the structural homologue to the CCA 3' end of tRNAs. Implications of C4 RNA processing for the lysis/lysogeny decision process of bacteriophages P1 and P7 are discussed.

Bacteriophage P1↗
PubMed1995

The lytic replicon of bacteriophage P1 is controlled by an antisense RNA.

The lytic replicon of phage P1 is used for DNA replication during the lytic cycle. It comprises about 2% of the P1 genome and contains the P1 C1 repressor-controlled operator-promoter element Op53.P53 and the kilA and the repL genes, in that order. Transcription of the lytic replicon of P53 and synthesis of the product of repL, but not kilA, are required for replicon function. We have identified an additional promoter, termed P53as (antisense), at the 5'-end of the kilA gene from which a 180 base transcript is constitutively synthesized and in the opposite direction to the P53 transcript. By using a promoter probe plasmid we show that transcription from P53 is strongly repressed by the C1 repressor, whereas that of P53as remains unaffected. Accordingly, the C1 repressor inhibits binding of Escherichia coli RNA polymerase to P53, but not to P53as, as shown by electron microscopy. Under non-repressed conditions transcription from P53 appears to be inhibited by P53as activity and vice versa. An inhibitory effect of P53as on the P1 lytic replicon was revealed by the construction and characterization of a P53as promoter-down mutant. Under non-repressed conditions transcription of repL and, as a consequence, replication of the plasmid is strongly enhanced when P53as is inactive. The results suggest a regulatory role for P53as on the P1 lytic replicon.

Bacteriophage P1↗
PubMed1995

Impact of polymorphisms in the alpha- and beta-fibrinogen gene on plasma fibrinogen concentrations of coronary heart disease patients.

Despite many investigations in a variety of experimental settings, uncertainty remains concerning the size of the genetic contribution to plasma fibrinogen levels. We used the polymerase chain reaction to amplify the polymorphic sites for the restriction enzymes TaqI in the alpha-fibrinogen gene and HaeIII, HindIII and BclI in the beta-fibrinogen gene. Three hundred and eighty-four male coronary heart disease patients were investigated. Two alleles for each enzyme (+ or - designating, respectively, the presence or absence of the cutting site) were detected. The HaeIII and HindIII cutting sites were in complete linkage disequilibrium. A small but significant increase in fibrinogen level was associated with the rare cutting sites of HaeIII/HindIII, BclI and TaqI. At all polymorphic sites homozygosity for the frequent alleles was associated with about 0.20 g/l lower plasma fibrinogen concentrations than heterozygosity at the respective sites (p < 0.05). The frequencies and natures of the rare alleles were as follows: TaqI (+) 0.28, HaeIII/HindIII (-) 0.22 and BclI (+) 0.17. Mean fibrinogen levels in patients heterozygous for each of the four polymorphisms were 0.47 g/l greater than in subjects homozygous for the frequent allele at each cutting site (HaeIII/HindIII + -, TaqI + -, BclI + -: fibrinogen level 3.58 g/l (n = 32); HaeIII/HindIII + +, TaqI - -, BclI - -: fibrinogen level 3.11 g/l (n = 99), p = 0.003). Each polymorphism accounted for between 0.5 and 1.4% of the overall variance in fibrinogen concentration. Together, the polymorphisms in HaeIII, HindIII and TaqI explained 5.8% of overall variance, a proportion equivalent to that explained by age, smoking and body mass index (5.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Brief clinical report: interstitial deletion of the long arm of chromosome 4, del(4)(q28-->q31.3).

Interstitial deletions of the long arm of chromosome 4 are rare. Different breakpoints are involved. Only one of the patients had a very similar deletion to that of the present case. Both had low birth weight at term; weight, length and head circumference less than the third centile; epicanthic folds; apparently low-set abnormal ears; broad nasal bridge; micrognathia; hypoplastic nails; delayed psychomotor development; and mild mental retardation.

Abnormalities, Multiple↗
PubMed1995

Reduction of tissue edema by microdialysis.

OBJECTIVE: This is the first report (to our knowledge) of the use of tissue microdialysis to reduce tissue edema. In this study, a hyperosmotic solution was perfused through microdialysis catheters, allowing direct treatment of interstitial edema by osmosis. DESIGN: First, the catheter and perfusate characteristics were tested in vitro. A physiologic, controlled trial was then performed, with two outcome variables: osmolarity of the effluent and tissue water content. SUBJECTS: Twenty male Sprague-Dawley rats. One rat was withdrawn. INTERVENTIONS: Tissue microdialysis catheters were implanted in the rats. The control side of the animals was not perfused. The experimental side was perfused for 9 hours. RESULTS: Osmolarity of the perfusate was reduced 16.5 mOsm after passing through the catheter, indicating that fluid was removed from the tissue. Tissue edema was reduced by an average 1.8 mL of fluid per 100 g of wet tissue. CONCLUSIONS: Tissue microdialysis removed tissue fluid and reduced edema. This treatment may have a beneficial effect on edematous tissues. Potential use and limitations of this therapeutic modality are discussed.

Animals↗
PubMed1995

The tripartite immunity system of phages P1 and P7.

Prophages P1 and P7 exist as unit copy DNA plasmids in the bacterial cell. Maintenance of the prophage state requires the continuous expression of two repressors: (i) C1 is a protein which negatively regulates the expression of lytic genes including the C1 inactivator gene coi, and (ii) C4 is an antisense RNA which specifically inhibits the synthesis of an anti-repressor Ant. In addition, C1 repression is strengthened by lxc encoding an auxiliary repressor protein. The repressors C1, C4 and Lxc are components of a tripartite immunity system of the two phages. Here, the mode of action of these regulatory components including their antagonists Coi and Ant is described.

Bacteriophage P1↗
PubMed1995

Measurement of acidic aerosol species in eastern Europe: implications for air pollution epidemiology.

A large number of studies have indicated associations between particulate air pollution and adverse health outcomes. Wintertime air pollution in particular has been associated with increased mortality. Identification of causal constituents of inhalable particulate matter has been elusive, although one candidate has been the acidity of the aerosol. Here we report measurements of acidic aerosol species made for approximately 1.5 years in Erfurt, Germany, and Sokolov, Czech Republic. In both locations, the burning of high-sulfur coal is the primary source of ambient air pollution. Twenty-four-hour average measurements were made for PM10, [particulate matter with an aerodynamic diameter (da) < or = 10 microns], as well as fine particle (da < 2.5 microns) H+ and SO4(2-) for the entire study. Additionally, separate day and night measurements of fine particle H+, SO4(2-), NO3-, and NH4+ and the gases, SO2, HNO3, HONO, and NH3 were collected with an annular denuder/filter pack system over a 7-month (late winter-summer) period with additional measurements during pollution episodes the following winter. At both sites, 24-hr SO2 (mean concentrations of 52 micrograms/m3, with peak levels of > 585 micrograms/m3) and PM10 (mean concentration 60 micrograms m3) concentrations were quite high. However, aerosol SO4(2-) concentrations (mean concentration of approximately 10 micrograms/m3) were not as great as expected given the high SO2 concentrations, and acidity was very low (mean concentration of < 1 microgram/m3, with peak levels of only 7 micrograms/m3). Low acidity is likely to be the result of NH3 neutralization and slow conversion of SO2 to SO4(2-).(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗
PubMed1995

Health effects of high level exposure to traditional pollutants in East Germany--review and ongoing research.

In East Germany ambient air pollution is characterized by high concentrations of sulfur dioxide (SO2) and suspended particulates (SP). Since acidity and sulfate are surprisingly low, oxidation of SO2 seems to be incomplete and neutralization seems to play an important role. Few studies on health effects of air pollution in the former German Democratic Republic have been performed. They showed an increased prevalence in polluted areas of respiratory symptoms, lung function decrement, mild anemia, nonspecific stimulation of the immune system and, retardation of skeletal maturation of children. Since the German unification in 1990, several large-scale studies have been started. Short-term effects of air pollution on daily mortality have been investigated in Erfurt retrospectively for 1980 to 1989. Logarithmic exposure-effect curves have been found for both SO2 and SP. The number of deaths increased by about 10% with SO2 and by more than 20% with SP if the 95th percentile of the pollutant is compared to the 5th percentile. The logarithmic shape shows that the increase of ambient concentrations at the beginning of the heating season in fall is more important than further increases in concentrations later in winter. A second study on short-term effects was conducted using daily peak flow measurements and respiratory symptoms in 270 patients with asthma and other obstructive airway diseases in East Germany and the Czech Republic between 1990 and 1992. From regression analysis it follows that an increase by 500 micrograms/m3 of SO2 leads to a mean decrease of the average patient's peak flow below 2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗
PubMed1995

Fibrinogen and cardiovascular risk.

Ischaemic heart disease and stroke are the major causes of death in the Western world. Established risk factors such as smoking, hypertension and hypercholesterolaemia explain only some of these events. Most myocardial infarctions and cardiac deaths are precipitated by acute occluding coronary thrombi, and it has been known for some time that thrombosis participates in atherogenesis. For these reasons, haemostatic variables have been included in studies of cardiovascular risk. The plasma fibrinogen level is associated with both the severity and the extent of coronary, cerebral and peripheral atherosclerosis. In prospective studies, fibrinogen was found to be an independent predictor of myocardial infarction in both sexes and of stroke in men. The plasma fibrinogen level thus provides information on risk over and above that supplied by established risk factors. Fibrinogen may play a part in atherothrombosis via several mechanisms: (1) by promoting atherosclerosis, (2) as an essential component of platelet aggregation, (3) because the amount of fibrin deposited and the size of the clot are directly related to the plasma fibrinogen level and (4) because fibrinogen increases plasma viscosity. Nevertheless, it is not yet possible to determine whether high fibrinogen levels are a cause or a consequence of cardiovascular disease because no drugs that selectively lower plasma fibrinogen levels are available. In addition, further standardization of measurements is needed before routinely including plasma fibrinogen in cardiovascular risk scores.

Animals↗
PubMed1995

Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain.

We investigated the vessel status of coronary and peripheral arteries and those arteries supplying the brain in 929 consecutive male patients admitted to a coronary rehabilitation unit. The severity of coronary atherosclerosis was scored using coronary angiography. Changes in extracranial brain vessels and manifest cerebrovascular disease (CVD) were determined by B-mode ultrasound and Doppler examination. Peripheral arterial disease (PAD) was diagnosed using base-line and stress oscillography. We assessed variables of coagulation, fibrinolysis, and the acute phase response. There was a significant increase in plasma fibrinogen, plasminogen, d-dimer and C-reactive protein (CRP) with increasing severity of coronary heart disease. Compared to men with unaffected arteries, men with 3 diseased coronary arteries had 58% greater d-dimer concentrations. Patients with CVD and PAD, respectively, also had significantly higher fibrinogen, d-dimer and CRP concentrations. We did not find an association between plasminogen activator inhibitor activity and the severity of coronary atherosclerosis. In conclusion, plasma fibrinogen, d-dimer and CRP concentrations were significantly related to atherosclerosis in the coronary, peripheral and extracranial brain arteries.

Acute-Phase Reaction↗
PubMed1995

[Isolation of the agent of European swine plague from imported frozen wild boar meat].

Since July 1993 imported frozen meat of wild boars has to be screened for the presence of HCV. The number of taken samples is given by the Ministry of health, sport and consumer protection. Until August 1994 the total number of 688 samples from different countries, have been examined. Three of them were found positive for HCV. The first one (November 1993) was from China, the other two positive samples were sent in one delivery from Romania in May 1994.

Animals↗
PubMed1994

Monocyte chemotactic protein-2, monocyte chemotactic protein-3, and fibroblast-induced cytokine. Three new chemokines induce chemotaxis and activation of basophils.

Cytokine-dependent mediator release from basophils and mast cells may play an important role in the pathogenesis of allergic and inflammatory conditions. Many C-C chemokines have been found to activate basophils and mast cells. We investigated the effect of three newly identified C-C chemokines, monocyte chemotactic protein-2 and -3 (MCP-2, MCP-3) and fibroblast-induced cytokine (FIC) on basophils and mast cells. We found that all three cytokines induced histamine secretion from basophils in a dose-dependent manner. The secretion of histamine was a Ca(2+)-dependent process. MCP-3 was the most potent activator of basophils. MCP-3 and FIC activated basophils from all study subjects, whereas the histamine release by MCP-2 was donor-dependent. The histamine-releasing activity of MCP-2, MCP-3, and FIC was compared with that of MCP-1, RANTES, and macrophage inflammatory protein-1 alpha using basophils from 10 donors. MCP-1 was the most potent among all the C-C chemokines. However, MCP-3 was nearly as potent. MCP-2, MCP-3, and FIC induced significant chemotaxis of basophils. None of the cytokines activated mouse peritoneal mast cells. The synthesis of mRNA for MCP-3 was investigated by reverse-transcription PCR using allergen-stimulated PBMC and bronchoalveolar lavage cells. Both MNC and bronchoalveolar lavage cells expressed mRNA for MCP-3. The results of this study indicate that MCP-2, MCP-3, and FIC are novel histamine-releasing factors.

Allergens↗
PubMed1994

Respiratory effects and tolerability of Mr 2264 Cl. A new opiate partial agonist in comparison with morphine and placebo.

In this double-blind, randomised, placebo-controlled cross-over study the respiratory effects of M(r) 2264 Cl 2 x 5 mg i.v., a new partial opiate receptor agonist, were investigated and compared with the respiratory effects of morphine 2 x 10 mg i.v. and placebo. As primary end-points, the slope of the rebreathing curve (dV'/dPCO2ET) and V55 (ventilation at PCO2ET = 55 mm Hg) were determined by Read's rebreathing method. The incidence of adverse events was also documented and compared. The respiratory depression after the intravenous administration of 5 mg and 10 mg M(r) 2264 Cl was comparable to the decreased sensitivity of the respiratory centre after the 20 mg morphine i.v. In contrast to morphine, a ceiling effect of M(r) 2264 Cl was found. The tolerability of M(r) 2264 Cl was comparable to that of morphine.

Adult↗
PubMed1994

Nuclear transport of U1 snRNP in somatic cells: differences in signal requirement compared with Xenopus laevis oocytes.

The signal requirement for the nuclear import of U1 RNA in somatic cells from different species was investigated by microinjection of both digoxygenin-labeled wild type and mutant U1 RNA molecules and in vitro reconstituted U1 snRNPs. U1 RNA was shown to be targeted to the nucleus by a temperature-dependent process that requires the prior assembly of RNPs from the common proteins and the microinjected RNA. Competition in the cell between immunoaffinity-purified U1 snRNPs and digoxygenin-labeled U1 snRNPs reconstituted in vitro showed that the transport is saturable and should therefore be a mediated process. The transport of a karyophilic protein under the same conditions was not affected, indicating the existence of a U snRNP-specific transport pathway in somatic cells, as already seen in the Xenopus laevis oocyte system. Surprisingly, the signal requirement for nuclear transport of U1 snRNP was found to differ between oocytes and somatic cells from mouse, monkey and Xenopus, in that the m3GGpppG-cap is no longer an essential signaling component in somatic cells. However, as shown by investigation of the transport kinetics of m3GpppG- and ApppG-capped U1 snRNPs, the m3GpppG-cap accelerates the rate of U1 snRNP import significantly indicating that it has retained a signaling role for nuclear targeting of U1 snRNP in somatic cells. Moreover, our data strongly suggest that cell specific rather than species specific differences account for the differential m3G-cap requirement in nuclear import of U1 snRNPs.

Animals↗
PubMed1994

Indoor factors and IgE levels in children.

The objective of the study was to determine indoor characteristics of households in relation to total serum IgE. In a population-based cross-sectional study, 1096 6-12-year-old children were examined in three East German towns (Eisleben, Hettstedt, and Zerbst). Of the questionnaires, 772 (70.4%) were returned by the parents. Serum IgE of 703 children and urinary cotinine in a random subsample of 224 children were analyzed. Linear regression on log(IgE) adjusted for the main covariates was used to assess indoor risk factors such as room size, and the presence of curtains, carpet, and plants in the child's room. Open-heating facilities indoors, passive smoking, and furniture made of chipboard had the most important effect. A higher urinary cotinine/creatinine ratio was associated with higher total IgE level. Total IGE increased also with the number of persons living in the household, independently of indoor smoking. We conclude that indoor air pollution from smoking and open-heating facilities may increase the IgE levels of children. The role of other factors such as chipboard, which could reflect the emission of formaldehyde, or the number of persons per household, which could reflect viral or helminthic infection, remains to be analyzed.

Air Pollution, Indoor↗
PubMed1994

Second-site suppressors of the bacteriophage P1 virs mutant reveal the interdependence of the c4, icd, and ant genes in the P1 immI operon.

The immI operon of phage P1 contains the genes c4, icd, and ant, which are transcribed in that order from the same constitutive promoter, P51b. The gene c4 encodes an antisense RNA which inhibits the synthesis of an antirepressor by acting on a target ant mRNA. Interaction depends on the complementarity of two pairs of short sequences encompassing virs+ and the ribosome-binding site involved in ant expression. Accordingly, in a P1 virs mutant phage, antirepressor is synthesized constitutively. We have isolated lysogen-proficient, second-site suppressors of P1 virs in order to evaluate the interdependence of the immI-specific genes. From a total of 17 suppressors analyzed, 15 were found to be located in the icd gene. They were identified as frameshift mutations, containing base insertions or deletions in tandem repeats of a single base pair. One suppressor was identified as a P51b promoter-down mutation; the second site of another suppressor was found to be located in the c4 gene. Furthermore, it was shown that virs cannot be suppressed by ant (icd+) suppressors. The results confirm the model that the immI operon is transcribed as a unit, that the icd and ant genes are translationally coupled, and that the constitutive synthesis of Icd protein alone is lethal to the bacterial cell. The existence of a c4 suppressor of virs, whose effect is not yet known, points to a still more complex regulation of antirepressor synthesis than was anticipated from the model.

Bacteriophage P1↗