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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

[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↗

NHE3: a Na+/H+ exchanger isoform of renal brush border.

Na+/H+ exchangers in the brush-border (luminal, apical) membrane of renal proximal tubules are responsible for active, transcellular reabsorption of NaHCO3 and NaCl. Although well characterized kinetically, the protein that mediates Na+/H+ exchange in the renal brush border has not been identified. Several Na+/H+ exchanger genes, including NHE1, NHE2, NHE3, and NHE4, are expressed in the kidney. To identify the NHE3 gene product and to determine its cellular and subcellular localization in the rabbit kidney, an NHE3-isoform-specific antibody was prepared. Guinea pigs were immunized with purified fusion protein containing the carboxy-terminal 40 amino acids of NHE3 (fpNHE3-C40). After affinity purification, immune sera demonstrated specific reactivity to the NHE3 sequence within the fusion protein as well as to an 80-kDa polypeptide expressed in NHE3-transfected LAP1 cells. Western blot analysis showed that anti-fpNHE3-C40 specifically reacted with an 80-kDa protein that is relatively enriched in renal brush-border membrane compared with basolateral membrane. Immunocytochemical studies confirmed that the Na+/H+ exchanger isoform NHE3 is expressed along the microvillar membrane of the brush border of proximal tubule cells in the rabbit kidney.

Animals↗

Behaviour in the novel environment predicts responsiveness to d-amphetamine in the rat: a multivariate approach.

The behaviour of rats in a novel environment was studied using a rapid time-sampling observation procedure followed by a principal component analysis (PCA) of the data. This approach revealed that novel environment behaviour can be described by two factors or principal components. The first factor comprised rearing, sniffing-up, ambulation and locomotion (photocell counts), and was termed "Escape". The second factor, which had high positive loadings of sniffing-down and locomotion and a high negative loading of immobility, was termed "Exploration". The scores of individual rats on the "Escape" factor predicted the stimulatory effect of acutely administered d-amphetamine (1.5mg/kg) on unconditioned behaviour. "Escape" high responders (HRs) showed more behavioural stimulation than "Escape" low responders (LRs). However, the locomotor stimulatory response of both groups increased after long-term, periodic administration of d-amphetamine and drug discrimination training, such that the level of drug-induced locomotor activity was now equivalent for the two groups. The same rats were tested twice with various doses of d-amphetamine after being trained to discriminate this drug (0.5mg/kg) from saline. "Escape" HRs were less sensitive than "Escape" LRs to the discriminative effects of 0.125-0.25mg/kg d-amphetamine. In contrast to these findings, "Exploration" HRs and LRs were not different on any of the dependent measures described above. These results are discussed in relation to the possibility that "Escape" factor scores are an indication of an animal's responsivity to novelty-induced stress. If this is the case, then animals which are more susceptible to the effects of novelty stress are more sensitive to the locomotor stimulating effects of acute d-amphetamine, but less sensitive to the cueing properties of low doses of this drug.

Journal Article↗

Immunocytochemical characterization of Na(+)-H+ exchanger isoform NHE-1 in rabbit kidney.

We have recently isolated cDNAs encoding a Na(+)-H+ exchanger isoform, referred to as NHE-1, from rabbit kidney and LLC-PK1 cells. To identify the NHE-1 protein and to establish its cellular and subcellular localization in the rabbit kidney, we prepared antibodies to a NHE-1 fusion protein. cDNA encoding the COOH-terminal 41 amino acids of NHE-1 was subcloned into a maltose-binding protein vector and the purified fusion protein (FP347A) used to immunize guinea pigs. To identify the NHE-1 protein, we performed Western blot analysis against membrane fractions prepared from rabbit renal cortex. Anti-FP347A antibody specifically reacted with a polypeptide with an apparent molecular mass of 100-110 kDa that was enriched in basolateral membrane fractions. When indirect immunofluorescence was performed on semithin (0.5 micron) cryosections of paraformaldehyde-lysine-periodate-fixed rabbit kidney, anti-FP347A specifically stained the basolateral plasma membrane of cells of the proximal tubule, thick ascending limb, and distal convoluted tubule. Anti-FP347A similarly stained connecting tubule cells and principal cells. No staining was detected on the apical membrane of any cells of the rabbit nephron. We conclude that NHE-1 is a 100- to 110-kDa protein expressed on the basolateral membrane of multiple nephron segments.

Animals↗

Agonist and antagonist activity of low efficacy D2 dopamine receptor agonists in rats discriminating d-amphetamine from saline.

The ability of the low efficacy D2 agonists preclamol and SDZ 208-911 to both antagonise, and substitute for, the d-amphetamine discriminative cue was investigated in rats trained to discriminate d-amphetamine (0.5mg/kg) from saline. All doses of preclamol (2.0-16.0mg/kg) and SDZ 208-911 (0.125-1.0mg/kg) only partially antagonised d-amphetamine discrimination. In contrast, the lower efficacy D2 agonist SDZ 208-912 completely blocked the cueing properties of d-amphetamine. Preclamol (4.0 and 16.0mg/kg) and SDZ 208-911 (1.0mg/kg) also partially substituted for d-amphetamine. In an additional study, the former drug enhanced the discriminative effects of a low dose of d-amphetamine (0.125mg/kg), whilst antagonising the effects of the training dose. Preclamol also partially antagonised the ability of the selective D2 agonist quinpirole (0.125mg/kg) to substitute for d-amphetamine. In contrast to the drug discrimination findings, preclamol completely antagonised the locomotor hyperactivity induced by acute d-amphetamine, in animals which had received the same long-term d-amphetamine treatment as the drug discrimination rats. The present findings reveal that preclamol and SDZ 208-911 can exert both agonist and antagonist activity in animals trained to discriminate d-amphetamine from saline. This partial agonist profile is probably due to the low efficacy D2 agonists interacting with a postsynaptic D2 receptor population possessing a higher response capability than those D2 receptors mediating d-amphetamine-induced locomotor hyperactivity.

Journal Article↗

[Case study of a Legionella epidemic in a rehabilitation clinic].

A series of nosocomial Legionella infections in a rehabilitation center is reported. In a three months period a total of 10 pneumonias with 3 deaths occurred (8 patients, 1 companion, 1 staff member). Serologic analysis proved additional Legionella infections within the nursing staff. The warm-water system was proved to be the source of infection by isolating Legionella pneumophila serogroup 1 subtype Pontiac both in warm-water and patients samples. The air conditioning system could not be ruled out as another (secondary) route of exposure because of shortcomings in construction. Conclusions about prevention and the course of the disease are discussed and standards for warm-water and air conditioning systems are proposed.

Adult↗

Role of dopamine D1 and D2 receptors in mediating the d-amphetamine discriminative cue.

The role of D1 and D2 dopamine (DA) receptors in mediating the discriminative cue produced by d-amphetamine (0.5 mg/kg) in rats has been assessed by using compounds which exert strong selectivity for each of these DA receptor subtypes. The D2 agonists quinpirole and RU 24213 substituted completely for d-amphetamine, while the D1 agonists SKF 38393 and SKF 81297 failed to exert such effects. On the other hand, the D2 antagonists raclopride and YM 09151-2, and D1 antagonists SCH 23390 and SKF 83566, all completely blocked d-amphetamine discrimination. The D2 antagonists produced more pronounced inhibitory effects on response rate than did D1 antagonists. Quinpirole substitution for d-amphetamine was blocked by YM 09151-2, but not by SCH 23390, while the locomotor stimulatory effect of quinpirole was inhibited by both drugs. The present findings confirm that D2 receptors play a primary role in the d-amphetamine discriminative cue, while the precise role of D1 receptors remains to be disclosed.

Animals↗

[Detection methods and occurrence of Cryptosporidium sp. in selected surface waters].

Cryptosporidium, a small coccidian parasite, is accepted as an important cause of severe diarrheal illness in man and animals; in immunocompromised persons illness may be life-threatening. Cryptosporidium is transmitted by oocysts, passed in the faeces. These oocysts are remarkable resistant to common disinfectants and they can survive for several months. Person-to-person, animal-to-person and faecal contaminations of the environment are proven routes of transmission. Also waterborne disease outbreaks caused by Cryptosporidium are well documented. This paper represents a modification of a method for the detection of Cryptosporidium in water, developed by Musial et al. and Rose et al. The method includes steps for filtration, elution, centrifugation, flotation and microscopic detection of Cryptosporidium oocysts in sediments using an indirect immunofluorescence technique and a native contrast-technique. With this modified method efficiency of recovery ranged from 8.1% to 27.1%. In addition, selected surface waters in Northrhine-Westphalia were examined. The finding of Cryptosporidium oocysts in 7 of 9 water samples (78%) demonstrates the occurrence of Cryptosporidium oocysts in surface waters in Western-Germany. These results suggest that more detailed studies are needed to assess the risk of this new pathogen in water, especially in removal and disinfection in water treatment plants.

Animals↗