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M Karolczak

Publications and source records attributed to M Karolczak.

15 recordsLinked to original sources
PubMed2001

Estrogen stimulates the mitogen-activated protein kinase pathway in midbrain astroglia.

Estrogen stimulates the development of midbrain dopamine neurons predominantly by acting through membrane receptors coupled to Ca(2+)-signaling. In this report, we describe that estrogen activates extracellular signal-regulated kinases (ERK1/2) in midbrain astrocytes but not neurons. This effect was inhibited by BAPTA which interrupts Ca(2+)-signaling but not by antagonists specific for other signaling pathways. The activation of the MAP kinase pathway suggests a potential role for astrocytes in mediating estrogen effects in the midbrain.

Animals↗
PubMed2001

Classical and nonclassical estrogen action in the developing midbrain.

There is widespread acceptance that estrogen is involved in various steps of cellular differentiation during brain development. In the past years, we have demonstrated such a developmental role for estrogen in the rodent midbrain. Precisely, estrogen affects midbrain dopamine neurons with respect to functional and morphological maturation. On the cellular level, estrogen may act classically by binding and activating its respective nuclear receptors, thereby controlling the transcription of target genes. On the other hand, many estrogen effects in the CNS are transmitted nonclassically by interactions with putative membrane receptors and by stimulating distinct intracellular signaling cascades. In the midbrain, classical and nonclassical estrogen signaling routes operate side by side to ensure the proper development of dopaminergic cells. In the present report, we detail some of the cellular and molecular events which are activated by estrogen and are thought to take part in the estrogen-mediated stimulation of dopamine neuron differentiation.

Animals↗
PubMed2001

Implementation of a cone-beam reconstruction algorithm for the single-circle source orbit with embedded misalignment correction using homogeneous coordinates.

We present an efficient implementation of an approximate cone-beam image reconstruction algorithm for application in tomography, which accounts for scanner mechanical misalignment. The implementation is based on the algorithm proposed by Feldkamp et al. and is directed at circular scan paths. The algorithm has been developed for the purpose of reconstructing volume data from projections acquired in an experimental x-ray micro-tomography (microCT) scanner. To mathematically model misalignment we use matrix notation with homogeneous coordinates to describe the scanner geometry, its misalignment, and the acquisition process. For convenience analysis is carried out for x-ray CT scanners, but it is applicable to any tomographic modality, where two-dimensional projection acquisition in cone beam geometry takes place, e.g., single photon emission computerized tomography. We derive an algorithm assuming misalignment errors to be small enough to weight and filter original projections and to embed compensation for misalignment in the backprojection. We verify the algorithm on simulations of virtual phantoms and scans of a physical multidisk (Defrise) phantom.

Algorithms↗
PubMed2000

Estrogenic stimulation of neurite growth in midbrain dopaminergic neurons depends on cAMP/protein kinase A signalling.

Previous work from this laboratory indicates that the differentiation of mouse midbrain dopaminergic neurons is influenced by estrogen. These effects may be transmitted either through classical nuclear receptors or via "nongenomic" mechanisms, including the interaction with hypothetical membrane receptors coupled to distinct intracellular signalling pathways. The latter mechanism seems to be of particular interest for the observed interactions of estrogen with developing dopaminergic neurons, insofar as estrogen has been shown to increase intracellular calcium levels within seconds. This study focuses on signal transduction cascades that might be activated by estrogen during differentiation of dopaminergic cells. Treatment with 17beta-estradiol or a membrane-impermeable estrogen-BSA construct (E-BSA) increased neurite growth and arborization of dopaminergic neurons. This effect was inhibited by antagonists of cAMP/ protein kinase A (PKA) and calcium signalling pathways but not by the estrogen receptor antagonist ICI. In addition, estrogen exposure stimulated the phosphorylation of CREB in midbrain dopaminergic cells as studied by quantitative double-labelling immunocytochemistry and gel shift assay. Again, this effect was antagonized only by the simultaneous treatment with inhibitors of the cAMP/PKA or calcium pathways and not by ICI pretreatment. These data together with our previous findings demonstrate that estrogen can interact with membrane binding sites on dopaminergic neurons, thereby stimulating the cAMP/PKA/phosphorylated cAMP-responsive element binding protein (CREB) signalling cascade, most likely through the activation of calcium-dependent kinases. In conclusion, rapid "nongenomic" estrogen signalling represents another mechanism, in addition to the activation of classical nuclear estrogen receptors, that is capable of influencing neuronal differentiation in the mammalian brain.

Animals↗
PubMed1999

Ontogenetic expression and splicing of estrogen receptor-alpha and beta mRNA in the rat midbrain.

Several studies have shown that estrogen is important for the differentiation of midbrain dopaminergic neurons. This is supported by the previous demonstration of estrogen synthesis in the perinatal ventral midbrain. The present study attempts to characterize the expression pattern of nuclear estrogen receptors (ER-alpha/beta) mRNAs in the ventral rat midbrain during development. By applying primers specific for the hormone-binding domain, ER-alpha mRNA was detected from embryonic day (E) 14 until postnatal day (P) 20, whereas considerable levels of ER-beta mRNA were found from P3 to P20. In contrast, primers spanning the DNA-binding domain demonstrated the presence of transcripts for ER-alpha as well as ER-beta after birth. These findings indicate that both ERs are expressed in the developing midbrain. The presence of ER-alpha transcripts devoid of the DNA-binding region is discussed in the context of 'non-genomic' estrogen signaling possibly by membrane receptors.

Animals↗
PubMed1999

[Micro-CT. Technology and application for assessing bone structure].

The strength and fracture resistance of bone is determined by the structure of the trabecular network and the cortical shell. While standard 2D techniques like histomorphometry are inadequate to assess the 3D nature of the trabecular network, isotropic 3D datasets of this network can be acquired with the new imaging modality of microCT. However, so far the quantitative analysis of the generated datasets, in particular the extraction of appropriate parameters describing the bone structure, has not been finally solved. In this article we describe the technology and applications of microCT systems relevant in the field of osteology. The most important technical features of current microCT systems in this context are: 1. A spatial resolution down to 5-10 microns can be achieved. 2. The maximum sample size is related to the desired resolution by a factor of approximately 1000, that is, a resolution of 10 microns limits the maximum sample size to approximately 1 cm. 3. Scan times for microCT systems vary between minutes and hours. Currently five areas for the application of microCT systems in osteology can be identified: 1. The search of parameters characterizing the 3D trabecular structure. 2. The application of finite element models to determine the biochemical competence of the structural parameters. 3. The use of microCT in preclinical trials to study drug effects in small animals. 4. The validation of analysis methods used in high-resolution in-vivo imaging systems. 5. The 3D quantification of modeling and remodeling processes.

Adult↗
PubMed1998

Developmental expression and regulation of aromatase- and 5alpha-reductase type I mRNA in the male and female mouse hypothalamus.

Androgen metabolites synthesized by neural aromatase and 5alpha-reductase are implicated in many aspects of mammalian brain development and, in particular, in the masculinization of distinct central nervous system structures and brain functions. The present study was designed to determine (1) the developmental profile of aromatase- and 5alpha-reductase type I mRNA expression in the mouse hypothalamus and (2) to relate ontogenetic sex differences in aromatase activity which have been described in the past to sex-specific aromatase gene expression. In addition, we analysed the effect of androgens on the perinatal regulation of hypothalamic aromatase and 5alpha-reductase type I mRNA expression. By applying semiquantitative reverse transcription-polymerase chain reaction analysis, we found hypothalamic aromatase mRNA expression to be developmentally regulated and to display sex differences at birth and on postnatal day 15 with higher mRNA levels in males. Newborn males and females, which were treated in utero with the androgen receptor antagonist cyproterone actetate, exhibited significantly reduced aromatase mRNA levels compared with untreated controls. In contrast to aromatase, expression levels of hypothalamic 5alpha-reductase mRNA did not reveal a clear-cut developmental profile or sex differences, and no regulatory role for androgens in controlling 5alpha-reductase mRNA expression was found. In conclusion, these results demonstrate perinatal sex differences in hypothalamic aromatase- but not 5alpha-reductase gene expression and suggest that sex differences in perinatal aromatase activity are reflected by corresponding differences in mRNA levels. Androgens are found to control brain estrogen formation pretranslationally at the level of aromatase gene expression. Our findings imply that sex differences in androgen availability and responsiveness are important regulatory factors for aromatase expression in the developing male hypothalamus.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1998

Developmental sex differences in estrogen receptor-beta mRNA expression in the mouse hypothalamus/preoptic region.

Estrogens play a significant role during mammalian brain development and are required for the masculinization of neuronal circuits involved in sex-specific behaviors and neuroendocrine functions. Cellular estrogen signalling is transmitted through nuclear estrogen receptors (ER) which are divided into two subforms: the ER-alpha as well as the recently cloned ER-beta have been demonstrated in the hypothalamus. In the present study, we have analyzed the sex-specific expression of ER-beta mRNA in the pre- and postnatal mouse hypothalamus/preoptic region (Hyp/POA) by semiquantitative RT-PCR. The ER-beta mRNA was detectable as early as embryonic day (E) 15 in the diencephalon of both sexes. In males, levels of mRNA expression in the Hyp/POA increased until birth and remained high throughout postnatal (P) development, whereas in females, such an increase was not observed. Significantly higher mRNA levels were detected in the male Hyp/POA from E17 until P15. Perinatal sex differences in ER-beta mRNA expression coincide with higher estrogen-forming rates in the male Hyp/POA. At present, no direct evidence is available which demonstrates that estrogen signalling through ER-beta is involved in brain development. However, data from our and other studies suggest a potential role for this signal transduction pathway for brain differentiation.

Animals↗
PubMed1996

[Polish "ZESPOL" osteosynthesis in diaphyses fractures in children].

Several variations of 52 original Polish "ZESPOL" osteosynthesis were employed in 50 children in bone diaphyses fractures treated at the 2nd dept. of Cardiac and General Pediatric Surgery. In 3 patients complex treatment was carried out by joined teams of 2nd dept. of the Cardiac and General Pediatric Surgery and Traumatology Ward of Niekłańska Street Pediatric Provincial Hospital, Warsaw. Follow-up period showed no early post-operative complications or bone healing disturbances. Excellent functional and cosmetic state of the operated extremities was preserved in all cases.

Child↗
PubMed1995

[Intrapericardial teratoma in a 3-month-old infant].

A 3-month-old infant with extensive intrapericardial teratoma compressing and dislocating the great vessels and the heart underwent successful surgery despite severe intraoperative circulatory disturbances.

Heart Neoplasms↗
PubMedDate not supplied

Steroid metabolising enzymes in the determination of brain gender.

The neurotrophic effects of oestrogen formed in the brain are important in brain sexual differentiation of the central nervous system and behaviour. Aromatase, converting testosterone to oestradiol-17beta, is a key enzyme involved in brain development. In primary cell cultures of foetal hypothalamus, we have found that male neurones consistently have higher aromatase activity than in the female. Using a specific antibody to the mouse aromatase, immunoreactivity was localized in the neural soma and neurites in hypothalamic cultures. Additionally more male foetal hypothalamus neurones express aromatase than in the female. Testosterone increases aromatase activity in parallel with a greater number of aromatase-immunoreactive neurones. Testosterone also increases soma size, neurite length, and branching of cultured hypothalamic neurones. The neuronal aromatase activity appears to be sensitive to the inductive effects of androgen only during the later stages of foetal development. Endogenous inhibitors of the aromatase are also likely to have a regulatory role. This work suggests that regulation of a network of aromatase neurones, sensitive to the hormonal environment of the hypothalamus, may determine when oestrogens are available for neurotrophic effects underlying brain differentiation.

Animals↗
PubMedDate not supplied

Estrogen: a multifunctional messenger to nigrostriatal dopaminergic neurons.

Gonadal steroids affect a wide variety of functions in the mammalian brain ranging from the regulation of neuroendocrine systems and the modulation of behavior to the stimulation of differentiation and plasticity of distinct neuronal populations and circuits. The last decades have also demonstrated that estrogen serves as a neuroprotective factor for distinct neurodegenerative disorders. Such neuroprotective effects of estrogen are most obvious for Parkinson's and Alzheimer's disease. Despite this knowledge, little is known about the mechanisms and cellular targets by that estrogen might elicit its protective influence. In the past, we have intensively studied the effects of estrogen on midbrain dopaminergic neurons which represent the most affected cell population during Parkinson's disease. These studies were mainly performed on developing dopaminergic cells and revealed that estrogen is an important regulator of plasticity and function of this neuronal phenotype. Precisely, we found that dopaminergic neurons are direct targets for estrogen and that estrogen stimulates neurite extension/branching and the expression of tyrosine hydroxylase, the key enzyme in dopamine synthesis. Together with other in vivo studies, we might draw the conclusion that estrogen is required for the plasticity and activity of the developing and adult nigrostriatal system. The presence of the estrogen-synthesizing enzyme aromatase within the nigrostriatal system further supports this idea. Surprisingly, estrogen effects on nigrostriatal cell function are not only transmitted by classical nuclear estrogen receptors but also depend on nonclassical estrogen actions mediated through putative membrane receptors coupled to diverse intracellular signaling cascades. In the future, it has to be elucidated whether nonclassical mechanisms besides genomic actions also contribute to estrogen-mediated neuroprotection in the adult CNS.

Animals↗