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Biomedical subjects

J Heinrich

Publications and source records attributed to J Heinrich.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1994

Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men.

Coronary thrombosis is regarded as the final occlusive event in the progress of coronary heart disease (CHD). Disturbances of the hemostatic system may favor this process and thus may indicate increased risk of myocardial infarction. Coagulation and lipid factors were measured in 2116 healthy male participants of the Prospective Cardiovascular Münster (PROCAM) study. After 6 years of follow-up, 82 coronary events (9 sudden cardiac deaths and 14 fatal and 59 nonfatal myocardial infarctions) were observed. The mean plasma fibrinogen levels of the event and nonevent groups differed by 0.25 g/L (2.88 [SD, 0.68] versus 2.63 [SD, 0.63] g/L, respectively; P = .001). The incidence of coronary events in the upper tertile of the plasma fibrinogen distribution was 2.4-fold higher than in the lower tertile. By multiple logistic function analysis, plasma fibrinogen was found to be an independent risk indicator for CHD (P < .05). Individuals in the high serum low-density lipoprotein (LDL) cholesterol tertile who also showed high plasma fibrinogen concentrations had a 6.1-fold increase in coronary risk. Unexpectedly, individuals with low plasma fibrinogen had a low incidence of coronary events even when serum LDL cholesterol was high. The mean factor VIIc activities in the event and nonevent groups did not differ significantly (112.3% [SD, 19.9] versus 108.4% [SD, 21.6]; P = .09). There was, however, a trend toward higher factor VIIc values when only fatal events were taken into account. Thus, higher levels of plasma fibrinogen markedly increased the predictive power of high serum LDL cholesterol. Low plasma fibrinogen is associated with low coronary risk even when LDL is raised.

Adult↗
PubMed1994

Effects of age, lipoproteins, and hemostatic parameters on the role of homocyst(e)inemia as a cardiovascular risk factor in men.

Previous studies have identified moderately elevated plasma concentrations of homocyst(e)ine as an independent risk factor for coronary heart disease (CHD). The atherogenicity of homocyst(e)ine has mostly been attributed to its effects on endothelial cells, platelets, and the hemostatic system. In this case-control study of 199 male CHD patients and 156 age-matched control subjects, we analyzed the role of homocyst(e)ine as a cardiovascular risk marker in the context of traditional risk factors as well as of plasma fibrinogen, plasminogen, and viscosity. Both univariate and multivariate regression analyses revealed that homocyst(e)ine levels were significantly correlated with age, fibrinogen, and plasma viscosity in both study groups. Geometric mean homocyst(e)ine levels by univariate analysis were significantly higher in patients than in control subjects (8.9 versus 7.8 mumol/L, P < .001). This difference remained significant on multiple logistic function analysis after being adjusted for body mass index, systolic blood pressure, serum cholesterol, and high-density lipoprotein cholesterol but not after additional adjustment for fibrinogen. By contrast, geometric mean fibrinogen levels after adjustment for homocyst(e)ine levels were significantly different between patients and control subjects (296.4 versus 230.8 mg/dL, P < .001). Within the group of CHD patients, both fibrinogen and homocyst(e)ine significantly increased in parallel with the number of stenosed coronary vessels. We conclude that hyperhomocyst(e)inemia is an independent coronary risk factor and that its interrelation with fibrinogen levels merits further study.

Adult↗
PubMed1994

Detection of early lung impairment with aerosol bolus dispersion.

The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by "pack-years" (PY). Smokers were classified into the following groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY < 10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.

Adult↗
PubMed1994

[Chlamydia infection and CIN].

Under the hypothesis that a chronic infection of the cervical epithelium leads to a reduction in the immunological response, a study was carried out to compare the possible relationship between chlamydial infection and CIN. 187 patients were referred to hospital for histological confirmation because of a cytological smear result (PAP III and IV a). Smears were examined for chlamydia antigens using immunofluorescence. The presence of antichlamydial IgA and IgG was performed in serum using an indirect immunohistochemical method. These tests confirmed CIN in 163 patients. The infection rate with chlamydia was 52.9%, 15.9% of CIN patients showing an active chlamydial infection. Inclusion of topographical findings, together with differential evaluation of colposcopic results, with reference to the transformation zone, allow for a separation between inflammation and dysplasia. The confirmation of a positive chlamydial infection and colposcopic criteria may help to reduce the high percentage of false-positive findings in the problem-group of PAP III patients. It appears that reservations about smear controls after doxycyclin therapy--including treatment of sexual partners--is justified.

Antibodies, Bacterial↗
PubMed1994

Factor VII-deficient substrate plasmas depleted of protein C raise the sensitivity of the factor VII bio-assay to activated factor VII: an international study.

Plasma from healthy individuals, pregnant women and patients on warfarin were distributed to 3 laboratories supporting major cardiovascular surveys (Northwick Park, Muenster and Houston) for assay of factor VII coagulant activity (VIIc) with their own bio-assays. The mean VIIc in 147 samples agreed to within 1% of standard in Northwick Park and Houston, but was 14% of standard lower in Muenster owing to its more potent standard. In samples with an increased VIIc the Northwick Park assay gave a higher result than the other assays owing to its increased responsiveness to activated factor VII (VIIa). Thus when VIIa concentrations were determined directly with a clotting assay which utilises a soluble recombinant tissue factor, the increase in VIIc with increase in VIIa was considerably greater with the Northwick Park assay than the Muenster assay. This feature of the Northwick Park assay was traced to the virtual absence of protein C in its substrate plasma. Factor Va appears rate-limiting for the coagulant expression of VIIa in test plasma. If the thrombotic response to release of tissue factor is determined by the circulating concentration of VIIa, then the Northwick Park factor VII bio-assay may be preferable to other bio-assays currently employed to estimate risk of acute coronary events.

Adult↗
PubMed1993

The antirepressor of phage P1. Isolation and interaction with the C1 repressor of P1 and P7.

Two antirepressor proteins, Ant1 and Ant2, of molecular weight 42 and 32 kDa, respectively, are encoded by P1 as a single open reading frame, with the smaller protein initiating at an in-frame start codon. Another open reading frame, icd, 5' upstream of and overlapping ant1 is required for ant1 expression. Using appropriate ant gene-carrying plasmids we have overproduced and purified Ant1/2 in the form of a protein complex and Ant2 as a single protein. Sequence analysis confirmed the N-terminal amino acids predicted from the DNA sequence of ant1/ant2, except that the N-terminal methionine is missing in the Ant2 protein. Under appropriate conditions the C1 repressors of phages P1 and P7 specifically co-precipitate with the Ant1/2 complex but not with Ant2 protein alone. The results suggest that the antirepressor may exert its C1-inactivating function by a direct protein-protein interaction.

Amino Acid Sequence↗
PubMed1993

Integration of biological and nursing sciences: a 10-year plan to enhance research and training.

A proposed multiyear plan of funding mechanisms by the National Center for Nursing Research (NCNR) to increase the use of biological theory and measurements in nursing research has been developed for both research training and research programs. The objectives of the research training programs are (a) to develop a cadre of nurse scientists with solid research training in the biological sciences, (b) to upgrade to state-of-the-art biological research for mid-career nurse scientists, and (c) to ensure adequate highly trained biological-nurse manpower will be available to accomplish the nation's nursing research agenda. The objectives of the research programs are (a) to stimulate nurse scientists to undertake novel, innovative research using state-of-the-art biological technology, (b) to link the behavioral and biological underpinnings of nursing science in specified areas of biomedical clinical research, and (c) to ensure that, in the coming decade, nursing science and behavioral research will be inextricably interwoven with biological research. The research training programs include: targeted predoctoral-postdoctoral transitional training, targeted predoctoral or postdoctoral fellowships, training awards for existing institutional training grants in other disciplines, mid-career awards, the Nurse Scientist award, and institutional training grants for biological nursing. The research programs include: small grants programs, augmentation of existing projects in other Institutes, Requests For Applications (RFA) in biobehavioral nursing, cluster studies, and clinical trials.

Awards and Prizes↗
PubMed1993

Cloning, expression, and characterization of the icd gene in the immI operon of bacteriophage P1.

The immI operon of P1 contains the genes c4, icd (formerly called orfx), and ant which are constitutively transcribed in that order from a single promoter, P51b. C4 is an antisense RNA which is processed from the precursor transcript. C4 RNA acts as a translational repressor of icd, thereby also inhibiting antirepressor (ant) synthesis. We have cloned the icd and the overlapping icd and ant genes. We show, by means of plasmid deletion analysis, that icd is translationally coupled to ant. An internal in-frame deletion of icd making up 65% of the codons still allows antirepressor synthesis at a reduced rate, indicating that a functionally active icd gene product is dispensable for ant expression. We identify the product of the icd gene as a 7.3-kDa protein which interferes with cell division. The results suggest that constitutive expression of icd, in the absence of a functionally active antirepressor, prevents P1 lysogen formation because of its detrimental effect on the host cell.

Bacteriophage P1↗
PubMed1993

Glutamine/histidine polymorphism in apo A-IV affects plasma concentrations of lipoprotein(a) and fibrin split products in coronary heart disease patients.

A glutamine/histidine polymorphism at residue 360 in apolipoprotein (apo) A-IV that generates two electrophoretically detectable isoforms, apo A-IV-1 and apo A-IV-2, affects the plasma concentration of lipoprotein(a) (Lp[a]) in a healthy population. To verify this unexpected association we analyzed the effect of the apo A-IV polymorphism on Lp(a) serum concentrations in 275 male coronary heart disease patients. Allele frequencies of apo A-IV-1 and apo A-IV-2 were 0.917 and 0.083, respectively. In addition, apo A-IV-1/2 heterozygotes showed a 30% lower geometric mean concentration of Lp(a) than apo A-IV-1/1 homozygotes in this study. The relative frequency of Lp(a) concentrations > 20 mg/dl was significantly increased by a factor of 2.25 in apo A-IV-1/1 homozygotes. Other lipid parameters were not significantly affected by this apo A-IV polymorphism. Because of the relations between Lp(a) and the fibrinolytic system, we also analyzed the effect of the apo A-IV polymorphism on hemostatic variables. Apo A-IV-1/2 heterozygosity was associated with a 70% higher geometric mean plasma concentration of D-dimer, i.e., proteolytic fragments of cross-linked fibrin. Plasma concentrations of prothrombin fragments F1 + F2, fibrinogen, plasminogen, and plasminogen activator inhibitor-1 were unaffected. In conclusion, our results indicate a hitherto unappreciated role of the apo A-IV gene or a closely linked locus for the regulation of Lp(a) metabolism and hemostasis and also possibly for atherosclerosis and thrombosis.

Apolipoproteins A↗
PubMed1993

Air pollution and daily mortality in Erfurt, east Germany, 1980-1989.

In Erfurt, Germany, unfavorable geography and emissions from coal burning lead to very high ambient pollution (up to about 4000 micrograms/m3 SO2 in 1980-89). To assess possible health effects of these exposures, total daily mortality was obtained for this same period. A multivariate model was fitted, including corrections for long-term fluctuations, influenza epidemics, and meterology, before analyzing the effect of pollution. The best fit for pollution was obtained for log (SO2 daily mean) with a lag of 2 days. Daily mortality increased by 10% for an increase in SO2 from 23 to 929 micrograms/m3 (5% quantile to 95% quantile). A harvesting effect (fewer people die on a given day if more deaths occurred in the last 15 days) may modify this by +/- 2%. The effect for particulates (SP, 1988-89 only) was stronger than the effect of SO2. Log SP (daily mean) increasing from 15 micrograms/m3 to 331 micrograms/m3 (5% quantile to 95% quantile) was associated with a 22% increase in mortality. Depending on harvesting, the observable effect may lie between 14% and 27%. There is no indication of a threshold or synergism. The effects of air pollution are smaller than the effects of influenza epidemics and are of the same size as meterologic effects. The results for the lower end of the dose range are in agreement with linear models fitted in studies of moderate air pollution and episode studies.

Air Pollutants↗