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Biomedical subjects

M Exner

Publications and source records attributed to M Exner.

At least 109 records · Page 6Linked to original sources

[Transmission of pathogenic human viruses by foods: hepatitis A epidemic caused by baked goods in the Euskirchen district)].

In the last few years many reports have documented that human pathogenic viruses are transmitted via food and can cause epidemics. Between November 1994 and February 1995 a HAV epidemic was recorded in the village and agricultural area of Euskirchen (Germany). 49 persons with HAV infections were registered. It seems that the epidemic started in a bakery and was caused by an employee who had spent his holidays in the Dominican Republic and came back already excreting the virus via his faeces. Two weeks later he developed a symptomatic illness. HAV is transmitted via a fecal-oral cycle. Lack of hygiene in food production and distribution cause the risk of secondary virus contamination. Virus transmission via food is first of all a problem in uncooked food. To ensure success in food safety in respect of foodborne human pathogenic viruses it is important to establish personal hygienic education, cleaning and disinfection plans and preventive measures such as immunization to avoid viruses in the food.

Disease Outbreaks↗

Lipoproteins accumulate in immune deposits and are modified by lipid peroxidation in passive Heymann nephritis.

Proteinuria in passive Heymann nephritis is primarily caused by reactive oxygen species that are produced by glomerular cells. Reactive oxygen species apparently exert their damaging effects on the glomerular filter by lipid peroxidation and subsequent adduct formation on matrix proteins of glomerular basement membranes. This raised the question as to the source of polyunsaturated fatty acids required as substrates for lipid peroxidation. Here we have localized by immunocytochemistry rat apolipoprotein E and apolipoprotein B within subepithelial immune deposits. Moreover, apolipoprotein B extracted from isolated glomeruli of proteinuric passive Heymann nephritis rats shows degradation and lipid peroxidation adduct formation, similar to apoproteins of oxidized lipoproteins in atherosclerotic lesions. These data provide evidence that lipoproteins accumulate within immune deposits and suggest that their lipids generate lipid-peroxidation-derived reactive compounds.

Animals↗

[Risk assessment and risk prevention in infectious diseases].

The purpose of risk assessment is to provide source data to state and local health agencies and other administrative departments to aid in the development of approaches for risk management and preventive strategies. In respect of the far reaching consequences it is necessary to have evaluated and accepted measures for the risk assessment. The system of risk assessment was developed in the USA for the assessment of chemical substances and includes the identification of the hazard, the exposure assessment, the dose-response-assessment and the risk assessment. Basis for the risk assessment are detailed information of the chemical substance or the pathogen and epidemiologic data. Preventive strategies and risk management like the stop of production have great social and economic consequences. Risk management must be highly effective. In a historic review it is described that in the past of the former centuries infectious diseases were tried to prevent or control in a wrong manner in consequence of the lack of knowledge about the etiology of infectious diseases. Since Robert Koch there was the beginning of an effective risk assessment and management of infectious diseases. Long time in this century it was thought that infectious diseases wouldn't play any role for the public health. Now it is clear that infectious diseases remain the leading cause of death and disability in the developed and underdeveloped countries and that the risk potential is increasing. Therefore risk-assessment and risk-management developed formerly for chemical substances are necessary for infectious diseases. Specific criteria for-the risk assessment for infectious diseases which are different to chemical substances are discussed like illness related, pathogen related, host related, transmission related factors and general aspects. The most important measures for risk management are discussed.

Communicable Disease Control↗

[Risk of exposure of children to indoor air allergens].

The development of allergic sensitization and disease in children depends mainly upon the genetic predisposition, the time and extent of exposure against allergens and upon environmental factors. Allergen avoidance in infancy substantially lowers the frequency of sensitization and allergic manifestations. In Germany mite allergens are the most important indoor allergens followed by cat allergens and fungal allergens. Private houses bear the greatest risk of exposure to mite allergens. Nevertheless in day nurseries there is a considerable amount of dust samples with mite allergen levels greater than 10 micrograms/g dust (18% of mattresses, 15% of soft toys, pillows etc.). Cat allergen levels in day nurseries and schools are similar to those in houses where a cat has never been kept. There is a correlation between the percentage of children who have cats at home and the cat allergen levels in dust. In an own study the mean numbers of fungal particles in dust samples from day nurseries were higher compared with those from private houses. Higher numbers of fungal particles concerned mostly day nurseries with flat roof and moisture problems. We conclude that generally private houses offer the highest risk of exposure to indoor allergens. In addition public places like day nurseries or schools must be taken into consideration as significant allergen sources.

Air Pollution, Indoor↗

Effects of the dopamine autoreceptor antagonist (-)-DS121 on the discriminative stimulus properties of d-amphetamine and cocaine.

(-)-DS121 [S-(-)-3-(3-cyanophenyl)-N-n-propyl piperidine) is a recently synthesised phenylpiperidine derivative suggested to be a dopamine receptor antagonist acting preferentially at dopamine autoreceptors. The drug exerts 'agonist-like' behavioural effects by enhancing dopamine release, but also shares properties in common with neuroleptics. The ability of (-)-DS121 to both generalise to and antagonise the stimulus effects of psychostimulants was determined in rats trained to discriminate d-amphetamine (0.5 mg/kg) or cocaine (5.0 mg/kg) from saline in a two-lever, food-reinforced, drug discrimination task. (-)-DS121 (3.5-14.0 mg/kg) produced small, but significant, increases in drug lever-appropriate responding in both d-amphetamine and cocaine-trained rats. However, there was no indication of a dose-dependent effect in either case. On the other hand, (-)-DS121 dose-dependently reduced response rate. Caffeine produced a higher level of drug lever-appropriate responding than (-)-DS121 in d-amphetamine-trained rats. (-)-DS121 (7.0-14.0 mg/kg) also weakly antagonised the cueing properties of both d-amphetamine and cocaine. A marked response disruption with the drug combination precluded testing of higher doses of (-)-DS121. A combination of subthreshold doses of (-)-DS121 (3.5 mg/kg) and d-amphetamine (0.0625 mg/kg) produced a significant degree of drug lever-appropriate responding, suggesting a synergistic interaction between these drugs. However, such an interaction was not noted with a higher dose of (-)-DS121, or when this drug was administered with a low dose of cocaine (0.25 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells.

Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a different, structurally related 130-kD membrane protein on the cell surface of renal microvascular endothelial cells are autoantigenic targets for ANCA in patients with active NCGN.

Amino Acid Sequence↗

Dental units: an environmental study of sources of potentially pathogenic mycobacteria.

SETTING: Infections caused by non-tuberculous mycobacteria (NTM) are generally thought to be acquired from environmental sources. However, little is known about the situations in which transmission occurs. OBJECTIVE: In an attempt to identify situations of relevant contact with NTM we investigated the water to which patients are exposed during dental treatment. DESIGN: The concentration and species of NTM were determined in 43 cooling and spray water samples from 21 dental units in ten offices. In addition, mycobacterial colonization of 16 biofilm samples from the waterlines of two dental units was investigated. RESULTS: The mean NTM concentration in the water samples was 365 colony-forming units (cfu) per mL, exceeding the mean drinking water concentration by a factor of almost 400. In the biofilm samples the mean NTM density amounted to 1165 cfu/cm2. The species identified included Mycobacterium gordonae, M. flavescens, M. chelonae, 'M. chelonae-like organism' and M. simiae. CONCLUSION: High numbers of NTM may be swallowed, inhaled or inoculated into oral wounds during dental treatment, possibly resulting in colonization, sensitization or infection. Mycobacterial proliferation in biofilms forming within dental units may explain the extent of NTM contamination of dental spray and cooling water.

Biofilms↗

Functional and regulatory analysis of the OmpF-like porin, OpnP, of the symbiotic bacterium Xenorhabdus nematophilus.

The function and novel regulation of OpnP of the symbiotic/pathogenic bacterium, Xenorhabdus nematophilus was studied. In vitro pore-function analysis of purified OpnP indicated that the single-channel-conductance values were similar to that measured for the porin protein, OmpF, of Esherichia coli. Nucleotide sequence analysis revealed that the mature OpnP protein contained 348 amino acid residues and shared 55% amino acid sequence identity with OmpF. Similar to ompF, opnP mapped between asnS and aspC. The 16 transmembrane beta-sheet structures and the internal loop 3 were highly conserved, while the remaining external loop domains were more divergent. Primer extension analysis identified the start site of transcription of opnP. A sigma 70-type promoter, a perfect 20 bp OmpR-binding site, and a binding site for the antisense molecule, micF RNA, were found in the upstream region of opnP. While the overall sequence identity of the asn-opnP-aspC region was high, the intergenic region between asnS and opnP had diverged markedly. The asnS-opnP region was 313 bp shorter than the intergenic region between asnS and ompF and lacked the OmpR-binding site that is required for ompF repression by high osmolarity in E. coli. Results from osmolarity-shift experiments indicated that OpnP was not repressed by high osmolarity. It was also found that OpnP was thermally regulated.

Amino Acid Sequence↗

[Risk of infection in endoscopy].

Infection is one of the hazards of endoscopic procedures. This long known risk has received major concern because of potential HIV infection. In the individual patient, both, patient related factors (such as the compromised host) and procedure related factors (such as tissue damage) determine the risk of infection. The potential for transmission of microorganisms from patient to patient or from the endoscopic equipment to the patient is reviewed. Common sources of infection and relevant microorganisms are listed. For prevention of transfer of infective agents through the contaminated endoscope the importance of thorough mechanical cleaning of the endoscope and adequate disinfection is stressed.

Cross Infection↗

[Preventing transmission of infection in endoscopy: hygienic maintainance of flexible endoscopes and measures for personal protection].

For prevention of transfer of infective agents by the contaminated endoscope the importance of thorough mechanical cleaning of the endoscope and adequate disinfection is stressed. Mode of action and side effects of liquid disinfectants as well as resistance of microorganisms (spores and some mycobacteria) to germicidal chemicals are mentioned. The different steps of disinfection procedures and potential causes of failure are discussed. Automatic disinfection systems are required for a higher degree of security of both patient and staff of the endoscopic unit. A regular control of the efficacy of the disinfection process is recommended and models for implementation are discussed. For prevention of occupationally acquired infection general precaution guidelines (use of gloves, prevention of needle-stick injuries) and vaccination programs are stressed.

Cross Infection↗

[Infectious diseases from the hygienic viewpoint with special reference to environmental infections--a retrospective and prospective view].

Infectious diseases showed a considerable change in their epidemiologic significance during this century. Twenty years ago it seemed that infectious diseases would be definity under control. As a result there was a neglect of the efforts for prevention, recognition and controlling of infectious diseases, especially in the administration. Today we have to state that old and new infectious diseases have regained a new and partly dramatic epidemiologic importance, influenced by several factors like overpopulation, wars, hunger, migration in the underdeveloped countries and the increase of the old and the immunosuppressed people of the population in the developed countries. A review is given of the increasing significance of old and new infectious diseases in the last 2 decades. Transmissible diseases from the environment have a special importance because many people are affected hereby. Hygienic aspects of drinking and swimming water, air- and ground caused infectious diseases are treated. The political support is requested. The institutions have had an important role in the prevention and control of infectious diseases in the past like the public health departments, hygiene and medical microbiologic urgently need the support and promotion of the government.

Communicable Disease Control↗

Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen.

Passive Heymann nephritis (PHN) is a model of human membranous nephropathy that is characterized by formation of granular subepithelial immune deposits in the glomerular capillary wall which results in complement activation. This is causally related to damage of the filtration barrier and subsequent proteinuria. The local accumulation of injurious reactive oxygen species (ROS) is a major effector mechanism in PHN. ROS may induce tissue damage by initiating lipid peroxidation (LPO). In turn, this leads to adduct formation between breakdown products of LPO with structural proteins, such as formation of malondialdehyde (MDA) or 4-hydroxynonenal-lysine adducts. To examine the role of LPO in the development of proteinuria we have localized MDA and 4-hydroxynonenal-lysine adducts in glomeruli of PHN rats by immunofluorescence microscopy, using specific monoclonal antibodies. By immunogold electron microscopy, MDA adducts were localized to cytoplasmic vesicles and cell membranes of glomerular epithelial cells, to the glomerular basement membrane (GBM), and also to immune deposits. Type IV collagen was specifically identified as being modified by MDA adducts, using a variety of techniques. Collagenase pretreatment of GBM extracts indicated that the NC-1 domain of type IV collagen was a site of adduct formation. When LPO was inhibited by pretreatment of PHN rats with the antioxidant probucol, proteinuria was reduced by approximately 85%, and glomerular immunostaining for dialdehyde adducts was markedly reduced, even though the formation of immune deposits was not affected. By contrast, lowering of the serum cholesterol levels had no influence on the development of proteinuria. These findings are consistent with the premise that ROS-induced glomerular injury in PHN involves LPO and that this results not only in damage of cell membranes but in modification of type IV collagen in the GBM as well. The close temporal correlation of the occurrence of LPO with proteinuria and the ability of probucol to inhibit proteinuria support a causal role for LPO in the the alteration of the glomerular permselectivity which results in proteinuria.

Aldehydes↗

[Digoxin content in blood lipids of children, athletes, sports ground attendants and residents after content with dioxin-containing surface slag (Kieselrot)].

In 1991 it was discovered, that a large number of sporting grounds and playgrounds in Germany were covered with a waste slag material from a former copper smelter located at Marsberg, Germany. This material was found to contain high levels of PCDD/F ranging up to 100,000 TE/kg. The objective of the present study was to assess whether subjects sporting on such grounds had elevated levels of PCDD/F in blood. PCDD/F in blood fat was used as an indicator of the PCDD/F body burden. Additionally, six children and seven residents of a contaminated sporting and playground were examined. Generally, the levels of PCDD/F in blood fat were in the range of background levels in all subjects. Taking into account the effect of age, slightly elevated blood levels of PCDD/F were detected in children. The results show that the bioavailability of PCDD/F in the slag material is very low. However, from the preventive point of view children who might ingest slag material by hand-to-mouth-activities, should not play on such contaminated playgrounds.

Adolescent↗

Antibodies to glycolipids activate complement and promote proteinuria in passive Heymann nephritis.

Passive Heymann nephritis is an experimental rat model of human membranous nephropathy induced by injection of antisera against crude renal cortical fractions such as Fx1A or rat tubular microvilli. This results in the formation of subepithelial immune deposits, the activation of the C5b-9 membrane attack complex of complement, and severe proteinuria. While the formation of immune deposits is attributed to in situ immune complex formation with antibodies specific for the gp330-Heymann nephritis antigenic complex (HNAC), activation of complement and proteinuria appear to be caused by at least one additional antibody species present in anti-Fx1A sera. We have separated by affinity absorption polyspecific antisera against Fx1A and rat microvilli into one IgG fraction directed specifically against microvillar proteins (anti-Fx1A-prot) and another IgG fraction specific for glycolipids (ant-Fx1A-lip) of tubular microvilli. When injected into rats, the anti-Fx1A-prot fraction induced immune deposits but failed to activate complement or produce proteinuria, similar to results obtained with affinity-purified anti-gp330 IgG. When the antibodies of the anti-Fx1A-lip fraction were injected alone they did not bind to glomeruli. By contrast, when the IgGs specific for the Fx1A-prot fraction (or for gp330-HNAC) were combined with those directed against the Fx1A-lip glycolipid preparation, immune deposits were formed, in situ complement activation was observed, and also proteinuria was induced. It is concluded that within anti-Fx1A and anti-microvillar sera there are at least two IgG fractions of relevance for the development of PHN: one directed against the gp330-HNAC complex which is responsible for the development of immune deposits, and a second specific for glycolipid antigen(s) which activate(s) the complement cascade.

Animals↗

Subtle variations in living conditions influence behavioural response to d-amphetamine.

The influence of prior living conditions on behaviours related to the reinforcing properties of d-amphetamine was determined. Rats were housed either in bright light (BL) conditions at the top of a standard rack or in dim light (DL) conditions on the third row of the same rack. Although BL rats showed a higher locomotor response in the novel environment, they were less sensitive than DL rats to the locomotor activating effects of d-amphetamine. The groups did not differ in responding for a secondary reinforcer in a conditioned reinforcement paradigm. However, only in DL rats as the response for the secondary reinforcer enhanced by d-amphetamine. These findings indicate that subtle differences in housing conditions can influence behavioural responses to psychoactive drugs.

Amphetamine↗