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Biomedical subjects

C Janke

Publications and source records attributed to C Janke.

17 recordsLinked to original sources
PubMed2002

Differential susceptibility of inbred mouse strains to Helicobacter pylori infection.

BACKGROUND: Host factors play an important part in the pathogenesis of Helicobacter pylori-associated disease. The aim of this study was to screen various inbred strains of mice for genetic differences in susceptibility to H. pylori infection. METHODS: Mice of strains BALB/cJ, C.B-17-Prkdc(scid), C3H/HeJ, C3H/HeN, C57BL/6J, C57BL/6J-I110(tm/Cgn), DBA/2J, and FVB/N were inoculated intragastrically with H. pylori SS1. At 1, 4 and 6 months after inoculation, mice were necropsied, and bacterial cultures and histologic studies of the stomachs were performed. RESULTS: Significant differences in the level of colonization by H. pylori were observed among inbred strains at each time of infection. These differences were most distinct at 4 months after inoculation with highest levels in strains C3H/HeJ and C3H/HeN and lowest in strains FVB/N, C57BL/6J and C57BL/6J-I110(tm/Cgn). Infected mice revealed a mild increase in inflammatory cells compared with controls at 1 and 4 months, but not at 6 months after inoculation. The host strain effect on gastric disease was fairly mild, with two exceptions. Firstly, infected I110(tm/Cgn) mice developed a severe, hyperplastic gastritis, indicating that interleukin-10 is an important regulator of the inflammatory response to H. pylori. Secondly, infected C3H/HeN mice had a propensity to develop lymphoid aggregates in the gastric mucosa. CONCLUSIONS: The strain differences described here will be useful for the design of genetic mapping studies in mice to elucidate the genes controlling gastric infection by H. pylori. Our results further show that genetically altered mice are a valuable tool for identifying candidate genes possibly contributing to susceptibility to H. pylori infection.

Animals↗
PubMed2001

The budding yeast proteins Spc24p and Spc25p interact with Ndc80p and Nuf2p at the kinetochore and are important for kinetochore clustering and checkpoint control.

Here, we show that the budding yeast proteins Ndc80p, Nuf2p, Spc24p and Spc25p interact at the kinetochore. Consistently, Ndc80p, Nuf2p, Spc24p and Spc25p associate with centromere DNA in chromatin immunoprecipitation experiments, and SPC24 interacts genetically with MCM21 encoding a kinetochore component. Moreover, although conditional lethal spc24-2 and spc25-7 cells form a mitotic spindle, the kinetochores remain in the mother cell body and fail to segregate the chromosomes. Despite this defect in chromosome segregation, spc24-2 and spc25-7 cells do not arrest in metaphase in response to checkpoint control. Furthermore, spc24-2 cells showed a mitotic checkpoint defect when microtubules were depolymerized with nocodazole, indicating that Spc24p has a function in checkpoint control. Since Ndc80p, Nuf2p and Spc24p are conserved proteins, it is likely that similar complexes are part of the kinetochore in other organisms.

Amino Acid Sequence↗
PubMed2001

Activation of mitogen-activated protein kinase cascade and phosphorylation of cytoskeletal proteins after neurone-specific activation of p21ras. II. Cytoskeletal proteins and dendritic morphology.

In the present study, we analysed changes in the expression, subcellular distribution and phosphorylation state of the microtubule-associated protein tau and other cytoskeletal proteins after neurone-specific activation of the mitogen-activated protein kinase (MAPK) in the CNS in vivo. We used transgenic mice with a neurone-specific expression of activated ras protein (p21H-ras(Val12), synapsin I promoter) that is associated with an augmented activity of the MAPK. Chronic activation of MAPK cascade influenced tau protein phosphorylation, localisation and dendritic morphology. While the amount of tau protein was elevated by 9%, phospho-epitopes detected by the monoclonal antibodies AT270, 12E8 and SMI34 were increased by about 21%, 40% and 59% respectively. Steady-state levels of tau mRNA were not affected. Thus, the increase in tau protein was most likely due to stabilisation of tau protein by augmented phosphorylation. While in wild-type animals tau protein was preferentially localised in axons, a prominent immunoreactivity was found in the somatodendritic compartment of transgenic mice. This subcellular translocation typically seen in pyramidal neurones was associated with an increase in the dendritic calibre by about 30% and is paralleled by an increase in tubulin of 19%. We were unable to obtain any morphological indication of neurodegenerative processes in these animals. We suggest that the moderate increase in tau protein and phosphorylation may be part of the neuroprotective mechanism. However, further studies on aged transgenic mice will be necessary to establish potential effects on neuronal viability.

Animals↗
PubMed2001

Hypertonic-hyperoncotic solutions decrease cardiac troponin I concentrations in peripheral blood in a porcine ischemia-reperfusion model.

In this study we addressed the question of whether the measurement of cardiac Troponin I (cTnI) is able to reflect beneficial effects of hypertonic-hyperoncotic solutions after transient cardiac arrest. Ten pigs were anaesthetized and cardiac arrest was induced by electric fibrillation. After 5 minutes of global ischemia, cardiac arrest was reversed by electric defibrillation. Upon return of spontaneous circulation 5 animals received hypertonic-hyperoncotic solutions (10% Hydroxyethylstarch 200/0.5 and 7.2% NaCl). The other animals received equivalent volumes of physiological saline. We observed that cTnI serum levels of animals treated with hypertonic-hyperoncotic solutions were significantly lower than those treated with saline. We conclude that hypertonic-hyperoncotic solutions may have cardioprotective effects.

Animals↗
PubMed2000

Cardiac troponin I and cardiac troponin T increases in pigs during ischemia-reperfusion damage.

In this study we addressed the question of whether the measurement of cardiac Troponin T (cTnT) and cardiac Troponin I (cTnI) is able to detect myocardial cell damage in an ischemia-reperfusion model in pigs. To answer the question 3 pigs were anaesthesized and a cardiac arrest was induced by electric fibrillation. After 5 minutes of global ischemia the cardiac arrest was reversed by electric defibrillation until normal perfusion was restored. We could clearly demonstrate an increase of cTnT and cTnI 30 minutes after reperfusion indicating myocardial injury during ischemia and subsequent reperfusion. The cTnT as well as the cTnI serum levels increased till 180 minutes after reperfusion. This ischemia-reperfusion injury is likely induced by oxygen radicals generated during hypoxia and subsequent reperfusion We conclude from our first results that troponin measurements with commercial available test kits may also reflect myocardial cell damage in pigs as it was recently demonstrated in rats. Further studies are needed for correlation of troponin serum levels and histopathological damage in this model especially if it is used to test beneficial or toxicological effects of radical neutralizing drugs.

Animals↗
PubMed2000

Analysis of the molecular heterogeneity of the microtubule-associated protein tau by two-dimensional electrophoresis and RT-PCR.

The microtubule-associated protein tau is a member of a group of proteins, promoting assembly and stabilization of microtubules. In several tauopathic neurodegenerative disorders, namely Alzheimer's and Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP 17) this protein is converted into fibrilar polymers which form the component of insoluble proteanous deposits such as neurofibrillary tangles. The formation of these fibrils is believed to interrupt the physiological function of neurons resulting in degeneration and cell death. Tau protein exists as a family of heterogeneous isoforms derived by both, differential splicing of tau-mRNA and posttranslational modification of the protein. Since the role of the different isoforms during the process of neurodegeneration is not well understood and as their balance might be altered in some cases of tauopathies (Spillantini et al., Proc. Natl. Acad. Sci. USA 1998;95:7737-7741), the detailed analysis of the molecular heterogeneity gained outstanding interest. The method presented here allows the analysis of both, differential splicing and phosphorylation of tau protein by the application of two-dimensional (2D) electrophoresis and Western blot detection. Tau protein isoforms could be identified from the 2D pattern of dephosphorylated tau in concordance with the results of tau-mRNA analysis by RT-PCR. The protocol presented was successfully applied to analysis of tau isoforms of human brain (Janke et al., FEBS Lett. 1996;379:222-226) and of several species, revealing a phylogenetic correlation of tau protein patterns in mammals (Janke et al., Mol. Brain Res. 1999;68:119-128). The present paper provides a detailed description of the technique and discusses its prospects and limits.

Animals↗
PubMed2000

Plasma homocysteine and lipoprotein profile in patients with peripheral arterial occlusive disease.

Several studies have identified moderate hyperhomocysteinemia (HCy) as an independent risk factor for atherosclerosis. The purpose of this case control study was to determine lipoprotein profile and homocysteine concentration in serum of 85 male patients with peripheral arterial occlusive disease (PAOD) and in 51 normolipidemic age-matched male controls. Cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol as well as subfractions HDL2 and HDL3 cholesterol, low-density lipoprotein (LDL) cholesterol, apo B, apo A-I, and lipoprotein particles LpA-I and LpA-I:A-II were measured in serum. Homocysteine, folic acid, and vitamins B6 and B12 were determined with the help of high-pressure liquid chromatography. The 677 C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was analyzed in PAOD patients. Patients with peripheral arterial occlusive disease showed a significantly higher mean concentration of homocysteine than control subjects (p<0.001). There was a negative correlation between the levels of homocysteine and vitamin B12 as well as folic acid (for vitamin B12: r=-0.40 and for folic acid: r=-0.38). The prevalence of hyperhomocysteinemia (Hcy >16 micromol/L) in the patients was 45% in contrast to 8% in controls. HDL cholesterol, HDL3 cholesterol, Apo A-I, and Lp A-I were significantly reduced in patients and triglycerides were elevated. The elevated plasma homocysteine concentration is frequently seen in homozygous carriers of a point mutation (677 C --> T) in the methylenetetrahydrofolate reductase gene, as the product of this gene is an enzyme, participating in homocysteine remethylation. The homozygous state for the 677 C --> T mutation was found in 13.3% of PAOD patients.

Aged↗
PubMed1999

Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders.

The microtubule-associated protein tau regulates the dynamic stability of the neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system. These isoforms differ in their ability to promote the assembly of microtubules as well as in their capacity to stabilize existing microtubule structures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau might critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The present study addresses the differential expression of the six isoforms of tau in the central nervous system of 12 mammalian species including Homo sapiens. The occurrence of each of the six tau isoforms was highly variable. However, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing paradigms, which can be matched with known phylogenetic concepts based on morphological and molecular genetical studies. Especially, the unique expression pattern of tau isoforms in the human central nervous system implicates a possible link to the particular vulnerability of humans to neurodegenerative disorders with tauopathy, namely Alzheimer's disease, frontotemporal dementia and Pick's disease.

Animals↗
PubMed1999

Comparison of caregivers', residents', and community-dwelling spouses' opinions about expressing sexuality in an institutional setting.

Opinions regarding the appropriateness of elderly residents' sexual behaviors in a chronic care hospital and how to respond to inappropriate behaviors were surveyed. Study participation was open to all staff (N = 1,205), eligible residents (N = 182) and community-dwelling spouses (N = 103). Participation rates were 40% (residents), 42% (spouses), 34% (nursing staff), 50% (allied health staff), and 22% (support staff). Staff completed the questionnaire independently, while residents and spouses were offered self-completion or a structured interview. Almost all selected the interview. Residents and spouses were less tolerant than staff of residents' masturbating, engaging in sexual relationships, viewing sexual materials, and making sexual approaches to staff. Privacy was the primary determinant of appropriateness for behaviors for all groups. Staff and spouses were more likely to endorse counseling when behaviors were perceived as inappropriate than residents. Nurses endorsed counseling less frequently than allied health professionals and support staff. Nurses were more likely to have been approached sexually by a resident. Differences of opinion are interpreted in terms of cohort influences on values and contextual influences on behavior.

Adult↗
PubMed1998

Reversible in vivo phosphorylation of tau induced by okadaic acid and by unspecific brain lesion in rat.

Alzheimer's disease (AD) is histopathologically characterised by the formation of neurofibrillary tangles (NFTs) that are largely composed of hyperphosphorylated tau protein (PHF-tau), and senile plaques which contain aggregates of the Abeta peptide. Formation of PHF-tau and amyloidogenic processing of the amyloid precursor protein (APP) might be related to a disturbance in the balance between protein phosphorylation and dephosphorylation. In the present study, the effects of injections into the cerebral cortex of either okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, or saline were investigated. Both kinds of injections induced a reversible phosphorylation of tau, albeit to a different extent. The secretion of soluble APP was reduced after OA but not affected after injection of saline. It is concluded that phosphorylation of tau, similar though not identical to those seen in AD can be induced in vivo by inhibition of protein dephosphorylation as well as by unspecific lesion of cortical neurones. It might, therefore, be suggested that phosphorylation processes involved in PHF-formation in AD similarly reflect a neuronal response to injury.

Animals↗
PubMed1998

Müller (glial) cells in the teleost retina: consequences of continuous growth.

In the continuously enlarging eye of teleost fishes retinal growth is achieved by the generation of new cells and by stretching the existing tissue. As a consequence of stretching, the density for most neurons decreases except for rod photoreceptors, which are produced by stem cells in the outer nuclear layer (ONL). We investigated retinal Müller glial cells with immunocytochemical markers against vimentin and glutamine synthetase in animals of various sizes. In addition, we used Western immunoblot analysis to investigate the changes in the glia-specific enzyme glutamine synthetase in the enlarging retina. We found that in the cichlid fish Haplochromis burtoni the density of Müller cells decreases from about 14 cells/mm2 to 4 cells/mm2 with increasing body size. Since it is known that the density of rod photoreceptors remains constant, it follows that the neuron to Müller cell ratio increases in the growing eye. In our estimates, this ratio ranges from around 54:1 in small fish to more than 67:1 in larger animals. Quantified Western blots revealed that the amount of glutamine synthetase per retinal area does not change in the growing eye, which means that the amount of this enzyme in each Müller cell must increase. Staining isolated cells and retinal sections from small and large fish with an antibody against glutamine synthetase showed stronger immunoreactivity in larger animals, especially in the areas of the photoreceptor cell bodies and outer limiting membrane and a more extensive branching of Müller cell processes. Thus, Müller cells in growing fish appear to compensate for the increasing metabolic challenge and are able to maintain their function.

Animals↗
PubMed1996

Distribution of isoforms of the microtubule-associated protein tau in grey and white matter areas of human brain: a two-dimensional gelelectrophoretic analysis.

The microtubule-associated protein tau in human brain consists of six molecular isoforms derived from a single gene by alternative mRNA-splicing and further modified by posttranslational processing. In the present study, the distribution of tau isoforms in grey and white matter of human temporal cortex was investigated by two-dimensional gelelectrophoresis. More than 80 isoforms were detected. The pattern of isoforms obtained after treatment with alkaline phosphatase was still more complex than those of recombinant tau, indicating that posttranslational modifications other than phosphorylation contribute to the molecular heterogeneity of tau. The tau isoform D according to Goedert containing four tubulin-binding regions shown to promote tubulin polymerisation most efficiently was present in higher amounts in white as compared to grey matter. The pattern of isoform distribution was not significantly altered in Alzheimer's disease. It is concluded that molecular isoforms that differ in their tubulin-binding characteristics are differentially distributed in subcellular neuronal compartments and/or neuronal types.

Alzheimer Disease↗
PubMedDate not supplied

Postmortem changes in the phosphorylation state of tau-protein in the rat brain.

The phosphorylation state of tau-protein is crucial for the regulation of neuronal microtubule organization. Functional conclusions on tau-protein require an accurate assessment of phosphorylated sites. Therefore, the in vivo distribution and postmortem preservation of some phospho-epitopes on tau-protein were examined in the rat brain under different fixation and preparation conditions. Detection of tau-protein with a phosphorylation-independent antiserum revealed both axonal and somatodendritic localizations, which were not influenced by a postmortem interval of 30 min. The phospho-epitopes recognized by 12E8, AT8, and PHF-1 were mainly localized in the somatodendritic compartment. The binding sites of AT8 and PHF-1 were rapidly dephosphorylated postmortem, whereas the Tau-1 epitope was unmasked in the somatodendritic region. The axonally located phospho-epitope of AT270 and the nuclear epitope of AT100 were still detectable after a postmortem interval of 30 min. Postmortem dephosphorylation and inhibition of this process by PP1 and/or PP2A was further demonstrated on Western blot. In conclusion, rapid processing of tau-protein is essential for the correct assessment of investigations on phospho-isoforms.

Animals↗