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Biomedical subjects

M Krupa

Publications and source records attributed to M Krupa.

At least 19 recordsLinked to original sources
PubMed2002

Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors.

Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH) have been found in several human cancer cell lines. GHRH antagonists inhibit growth of various human cancers, including osteosarcomas and Ewing's sarcoma, xenografted into nude mice or cultured in vitro and their antiproliferative action could be mediated, in part, through these SV of GHRH receptors. In this study, we found mRNA for the SV(1) isoform of GHRH receptors in human osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted by the cells, as shown by the presence of GHRH-like immunoreactivity in the conditioned media of cell cultures. In proliferation studies in vitro, the growth of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of an autocrine stimulatory loop based on GHRH and SV(1) of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV(1) of GHRH receptors on tumoral cells.

Alternative Splicing↗
PubMed2001

Dynamics of the membrana granulosa during expansion of the ovarian follicular antrum.

As an endocrine organ, the ovary has some unique characteristics. The formation, the maturation and the regression of the hormone producing cells really determine the timing, the amount and the type of hormone secreted. Here, we focus on the granulosa cells of ovarian follicles which express 17beta-hydroxysteroid dehydrogenase type 1 and cytochrome P450 aromatase. Follicles only produce estradiol late in follicular development before either ovulation or atresia ensues. We discuss the evidence that the membrana granulosa has many characteristics in common with other epithelia, including that it arises from stem cells. The corollary of this is that individual cells within the membrana granulosa are of different ages or stages of specialization. This is evident as regional differences across the membrana granulosa in terms of cell ages, shapes, gene expression, and even behaviour on cell death. We discuss theoretical considerations of the effects of antrum formation on the behavior of the membrana granulosa, and show evidence for differences between follicles in cell shapes, basal lamina phenotypes and location of younger cells, which we speculate is due to different rates of antrum expansion. Clearly, the membrana granulosa is dynamic, and this could explain much about the differences in the behaviors of cells from within the membrana granulosa, and between ovarian follicles.

17-Hydroxysteroid Dehydrogenases↗
PubMed2001

Targeting of doxorubicin to ES-2 human ovarian cancers in nude mice by linking to an analog of luteinizing hormone-releasing hormone improves its effectiveness.

Receptors for luteinizing hormone-releasing hormone (LHRH), expressed by ovarian cancers, can be used for targeting chemotherapeutic compounds more selectively to these tumors. We investigated the effects of cytotoxic LHRH analog AN-152, consisting of doxorubicin (DOX)-14-O-hemiglutarate linked to the epsilon-amino group of [D-Lys6]LHRH, on the growth of LHRH receptor-positive ES-2 human ovarian cancer line xenografted into nude mice. A single injection of AN-152, at a dose of 345 nmol/20 g body weight, caused a 34.5% reduction (P<0.05) in tumor growth after 28 days, while its cytotoxic moiety DOX was inactive at the same dose. Since the overexpression of certain growth factors and/or their receptors, such as vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and HER-2/neu, as well as various oncogenes like c-fos and c-jun, is associated with unfavorable prognosis and contributes to progressive growth of ovarian carcinomas, their mRNA levels were analyzed by RT-PCR. Treatment with AN-152 significantly (P<0.05) reduced the expression of EGFR, VEGF, c-fos and c-jun, to 49%, 48%, 55% and 58% respectively, compared to controls. HER-2/neu mRNA expression was also decreased to non-detectable levels. Conversely, DOX decreased non-significantly the expression levels for EGFR by 32%, VEGF 35%, both c-fos and c-jun approximately 20% and HER-2/neu by only 15%. In conclusion, cytotoxic LHRH analog AN-152 could be considered for chemotherapy of ovarian cancers expressing LHRH receptors.

Animals↗
PubMed2001

[Neurotrauma in treatment of nervous system injuries--principles in cooperating with anesthesiologists].

After brain trauma neuronal degeneration results due to the combination of primary mechanical disruption of CNS parenchyma and the secondary pathophysiological events. The fact that the treatment can modified the clinical course and the final outcome, implies that is indeed a modifiable secondary neurodegenerative process which is caused by the mechanical injury. Contemporary in patients with craniocerebral trauma and with polytrauma our management is focused on prevention of secondary brain injury. On the accident scene that is crucial to appropriate ventilate the patient, stabilize blood pressure and prevent shock. The diagnostic tool of choice is CT, but made in the very early stage could revealed false negative scan. That could be the cause of missed beginning of intracranial pressure increase in artificially ventilated patients. Multimodality monitoring in highly specialized centers could enable early detection of such increase (ICP) and help in estimation of indication for surgical treatment. The mechanism, direct sequelae of head trauma and neurological symptoms dynamics are also important.

Ambulatory Care↗
PubMed2000

Prenatal exposure to the dopamine agonist SKF-38393 disrupts the timing of the initial response of the suprachiasmatic nucleus to light.

The abuse of social drugs such as cocaine during pregnancy represents enormous risks to the offspring. Recent studies showed that drugs administered to the pregnant rat can activate cell populations in the fetal brain, possibly altering the timing of key neuronal developmental events. The current study examined the ontogeny of light-responsiveness of the neonatal rat suprachiasmatic nucleus using c-FOS protein in SCN nuclei as a marker. The effect of acute administration of the dopamine D1 agonist, SKF-38393, on the development of light responsiveness was also examined. Pregnant dams received either SKF-38393 (10 mg/kg) or vehicle 7 h after dawn on gestational day 20. Litters were then assigned to one of seven experimental time points from 4 h after subjective dark onset on the day of birth (P0-CT16) at 4-h intervals until CT16 on the day after birth (P1-CT16). Half of the pups in each litter were exposed to a 200 lux/2 h light pulse and the other half remained in darkness. Three time points (P1-CT0, P1-CT8 and P1-CT16) were used to examine the prenatal drug effects on light-responsiveness. Light exposure at the time of subjective lights on, the day after birth (P1-CT0), resulted in a significant increase in c-FOS-positive cells. The number of positive cells recorded in the SCN after a light pulse at P1-CT0 and P1-CT8 was significantly less in SKF-38393 pretreated pups compared to vehicle treated animals. The exposure to dopaminergic stimulation during gestation may have altered the timing of development of afferent connections to the fetal SCN, resulting in alteration of the initial response of the circadian timing system to light.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2000

[Post-traumatic bacterial meningitis].

10 patients with posttraumatic bacterial meningitis were treated in the Department of Infectious Diseases of the Jagielloniam University--Collegium Medicum during the period of 63 months. Traffic accidents were responsible for 80% of all cases of trauma. The most common place of injury was the base of anterior cranial fossa. Infecting agent was established in 8 cases. Gram-positive aerobic cocci (Streptococcus pneumoniae, Enterococcus faecalis, and Enterococcus spp.) were found in 4 patients, Gram-negative aerobic cocci (Neisseria meningitidis) in 2 patients, and Gram-negative aerobic rods (Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella spp, Escherichia coli) in 3 patients. Streptococcus pneumoniae was still highly sensitive to penicillin, ampicillin and cefotaxime. Enterococcus faecalis and Enterococcus spp. were sensitive to vancomycin and teicoplanin. Neisseria meningitidis was sensitive to penicillin, cefotaxime, amoxicillin/clavulonate. Gram negative aerobic rods were sensitive to third-generation cephalosporins, carbapenems and aminoglycosides. Among 10 patients treated for posttraumatic bacterial meningitis 1 patient died and in 1 preserved vegetative state was diagnosed. In 4 patients severe or moderate disabilities developed, however 4 recovered completely. 6 patients after regression of the CNS infection were qualified to neurosurgical intervention. In 3 patients reconstructive operation of the basis of anterior cranial fossa with tissue glue Beriplast P. was done, the recovery was complete. 3 patients didn't agree to surgical operation, and we don't know what has happened with them. They have not come to the control visit.

Adult↗
PubMed1999

Development of the membrana granulosa of bovine antral follicles: structure, location of mitosis and pyknosis, and immunolocalization of involucrin and vimentin.

The membrana granulosa of the ovarian follicle is termed the 'follicular epithelium', yet there have been no studies considering its epithelial nature and how it changes during follicular development. Therefore, these issues were investigated using histology (n = 45 ovaries), considering its structure and the location of proliferating and dying cells, and drawing analogies with other epithelia. Additionally, differences between the layers of granulosa cells were demonstrated by immunohistochemistry (n = 7 ovaries). The structure of the membrana granulosa differed between follicles. Six arbitrary classifications were designed based on these structures, 80 follicles were allocated (n = 13 ovaries) to these classes and the follicular diameters were then measured. For the first time, differences in membrana granulosa structure were shown to correspond to follicle size. Follicles in classes 1-3, where basal granulosa cells were columnar with nuclei positioned basally in the cell, were all < or = 3 mm in diameter. All follicles larger than 3 mm had either columnar basal cells with nuclei positioned centrally (class 4), or had rounded basal cells (class 5), and all follicles > 5 mm had only rounded basal cells. In all these classes, cells in the middle zone were rounded; cells aligning the antrum were often flattened. Irrespective of follicle class, cell proliferation and cell death were shown to be predominantly in the middle portions, rather than the most antral or most basal portions, of the membrana granulosa of healthy and atretic follicles. Involucrin, a marker of keratinocyte differentiation, was localized to the suprabasal region of the membrana granulosa of healthy follicles, particularly in the second and third cellular layers in from the follicular basal lamina. Conversely, the staining intensity for the intermediate filament protein vimentin was lowest in this region, and greatest in the more antral and basal regions. In atretic follicles, there was widespread staining for involucrin and vimentin throughout the membrana granulosa. In conclusion, the membrana granulosa is highly structured, and alters with follicular development. Layers in the membrana granulosa can differ in terms of cell shape, and differ in proliferation and gene expression. In the light of the current work, and an associated study, it is proposed that proliferation occurs in the middle layers, and that granulosa cells, then progress basally or antrally, the latter undergoing terminal differentiation.

Animals↗
PubMed1999

[Clinical observations concerning piracetam treatment of patients after craniocerebral injury].

Piracetam (Nootropil) is a cytoprotective to brain tissue and improving cerebral blood flow medicine. In the Department of Neurotraumatology we investigated results of piracetam treatment in a group of 100 succeeding patients admitted between 1995-96 due to craniocerebral injury. High doses (24-30 g per day) of this medicine have a positive effect on final result of treatment, when treatment is initiated immediately after the injury and described conditions are abided. We also showed usefulness of piracetam treatment in posthospital management.

Brain Injuries↗
PubMed1999

Roles of extracellular matrix in follicular development.

The cellular biology and changes in the extracellular matrix of ovarian follicles during their development are reviewed. During growth of the bovine ovarian follicle the follicular basal lamina doubles 19 times in surface area. It changes in composition, having collagen IV alpha 1-26 and laminin alpha 1, beta 2 and gamma 1 at the primordial stage, and collagen IV alpha 1 and alpha 2, reduced amounts of alpha 3-alpha 5, and a higher content of laminin alpha 1, beta 2 and gamma 1 at the antral stage. In atretic antral follicles laminin alpha 2 was also detected. The follicular epithelium also changes from one layer to many layers during follicular growth. It is clear that not all granulosal cells have equal potential to divide, and we have evidence that the granulosal cells arise from a population of stem cells. This finding has important ramifications and supports the concept that different follicular growth factors can act on different subsets of granulosal cells. In antral follicles, the replication of cells occurs in the middle layers of the membrana granulosa, with older granulosal cells towards the antrum and towards the basal lamina. The basal cells in the membrana granulosa have also been observed to vary in shape between follicies. In smaller antral follicles, they were either columnar or rounded, and in follicles > 5 mm the cells were all rounded. The reasons for these changes in matrix and cell shapes are discussed in relation to follicular development.

Animals↗
PubMed1989

Selective effects of serotonin upon excitatory amino acid-induced depolarizations of Purkinje cells in cerebellar slices from young rats.

The effects of serotonin on responses induced in Purkinje cells (PCs) by microiontophoretic administration of excitatory amino acids (EAAs) in their dendritic fields were tested in vitro by extracellular recording and by single electrode voltage clamp methods in cerebellar slices from rats aged 16-22 days. Serotonin diminished excitations produced by glutamate (Glu) and quisqualate (Quis) selectively, those caused by N-methyl-D-aspartate (NMDA) being affected much less. These suppressions of Glu- and Quis-induced responses generally occurred without there being any effect on intrinsic membrane properties of PCs, although on occasion serotonin increased membrane conductance slightly and/or induced an outward current in the recorded cells. All these effects of serotonin were maintained in the presence of tetrodotoxin and reversed upon removal of the amine. On the few occasions when serotonin enhanced Quis-induced responses, the effect was mimicked by ejection from a control solution of saline, made up at the same pH as the drug solution of serotonin.

Action Potentials↗
PubMed1988

Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study.

In immature rat cerebellar slices in vitro, a long term depression (LTD) of the responses of Purkinje cells (PCs) to L-glutamate (Glu) was achieved in 30% of the recorded cells by simultaneous stimulation of the neurones by Glu and by climbing fibres (CFs). This effect was not observed for L-aspartate (Asp)-induced responses. Similarly, selective LTD of Glu-induced responses was obtained in 22% of the cells by pairing Glu applications with direct stimulation of the cells which elicited calcium spikes in these neurones. Finally, bath application of phorbol esters also induced a selective LTD of Glu-induced responses in all cells tested. These results suggest that protein kinase C is involved in cerebellar synaptic plasticity.

Animals↗
PubMed1988

Development of ionic conductances in neurons of the inferior olive in the rat: an in vitro study.

Neurons of the inferior olive of the rat were studied at different stages of their postnatal (PN) development by using the current clamp technique in slices maintained in vitro. Antidromic and synaptic activation of inferior olivary neurons could be achieved in preparations as young as PN day 2. Neurons at this age already exhibited a variety of ionic conductances which included fast sodium-dependent spikes, high-threshold and low-threshold calcium spikes, potassium-dependent currents, Ca-dependent after-hyperpolarizing potentials (AHPS), and both instantaneous and time-dependent inward rectification at hyperpolarized levels of membrane potential. The two types of Ca-dependent responses recorded in olivary neurons during the first postnatal week were graded with the magnitude of the depolarization imposed on the cells. Furthermore, the high-threshold Ca spikes were only clearly observed during this early period when K conductances were depressed by the injection of caesium into the cells or by bath application of 4-aminopyridine. In contrast, the high-threshold Ca spikes could be obtained without suppression of K currents and were all-or-none in character in some neurons after PN day 8 and in all neurons after PN day 11. The observations suggest that the balance between K and Ca currents changes throughout maturation and is largely in favour of the K current until about the end of the first PN week. At all ages studied, the low-threshold Ca spikes were much less sensitive to the Ca channel blocker cadmium than were the high-threshold Ca spikes. Finally, spontaneous, regular oscillations of the membrane potential were observed for the first time at PN day 16 and were only commonly observed after PN day 19, suggesting a late development of electrotonic coupling between olivary neurons.

Aging↗
PubMed1987

Differential effects of serotonin on the spontaneous discharge and on the excitatory amino acid-induced responses of deep cerebellar nuclei neurons in rat cerebellar slices.

The effects of steady iontophoretic applications of serotonin on the spontaneous discharge and on the excitatory responses induced in deep cerebellar nuclei neurons by iontophoretic pulse applications of L-glutamate, L-aspartate, N-methyl-D,L-aspartate and quisqualate were studied in rat cerebellar slices maintained in vitro. Serotonin increased the spontaneous firing rate of deep cerebellar nuclei neurons in 91% of the tested cells by 109% on the average and had no effect on the remaining recorded neurons. Conversely, the monoamine induced a depression of the excitatory responses induced by four agonists tested and the depressant potency of serotonin was in the order quisqualate, glutamate, aspartate, N-methyl-D,L-aspartate. These effects persisted in low calcium high magnesium solution, suggesting that the serotonin receptors involved in these phenomena were, at least partially, postsynaptically located. The serotonin-induced increase in the cell firing rate appeared to be methysergide-resistant whereas the serotonin-induced decrease in the responses elicited by excitatory amino acids was depressed by this antagonist, which could indicate that these differential effects of serotonin are mediated via different mechanisms and/or serotonin receptor subtypes.

Action Potentials↗
PubMed1986

Visual localization and discrimination after ibotenic lesion of the cat orbito-insular cortex.

Behavioral tasks were used to investigate how the orbito-insular cortex (OIC) of the cat is involved in complex operations such as the orienting reaction towards a novel stimulus. Six cats were trained preoperatively on a perimetry test to assess their ability to orient the head and eyes to objects presented in restricted regions of the visual field, and on brightness, pattern and form discrimination tasks for food reward in a two-choice discrimination apparatus. Two animals then underwent unilateral chemical lesion of the OIC using injections of ibotenic acid, two others received bilateral lesions of this same area, and the remaining two cats were used as normal controls. Postoperative performance of brightness, pattern and form discrimination was normal following OIC lesions, and no lack of retention was observed. In contrast, the cats with OIC lesions had significant deficits in their visually guided behavior. The cats ignored objects presented in the monocular segment of both sides of the visual field, even after unilateral lesion, and there was an effect on the ability to attend and fixate the central preconditioned stimulus.

Animals↗
PubMed1984

Visual properties of neurons in the suprageniculate nucleus of the cat.

Visual response properties were studied in 83 single units recorded in the cat suprageniculate nucleus (Sg). About 70% of the cells were visually driven preferentially by the contralateral eye and triggered by moving stimuli without directional selectivity. Receptive fields were usually of a large size (greater than 20 degrees) and for half the cells, extended into both contralateral and ipsilateral fields of vision. No retinotopy nor functional clustering within the nucleus could be demonstrated. These properties of the visual neurons in the Sg nucleus are discussed in relation to the afferent and efferent connections of this nucleus.

Action Potentials↗
PubMed1983

An anatomical investigation of visual inputs to the cat orbital cortex.

The orbital region of the cortex in the cat is known to be involved in multimodal sensory functions. Visual afferent connections of this area have been investigated using the horseradish peroxidase technique. Our results demonstrate the existence of projections from ipsilateral thalamic nuclei essentially at the suprageniculate and magnocellular medial geniculate junction, well known to have multimodal physiological properties.

Afferent Pathways↗
PubMed1982

Identity problems concerning subunits of the membrane factor of the mitochondrial ATPase of Saccharomyces cerevisiae.

As confirmed by fingerprint analysis, high-resolution acrylamide gel electrophoresis identifies subunits of the mitochondrial ATPase complex directly at the level of Coomassie-blue-stained yeast mitochondria. Using this technique, the following results were obtained. 1. Three classes of subunits have been found in the ATPase complex. (a) The classical F1 peptides of cytoribosomal origin (57, 53 and 30.5 kDa). (b) Two peptides of mitoribosomal origin with high cycloheximide-resistant label: one of 7.8 kDa (the OLII gene product), the second of 20 kDa (the OLI2 gene product). Neither of these peptides is readily stained by Coomassie blue in the purified ATPase complex, (c) Four Coomassie-blue-stained peptides (27.5, 25, 23.5 and 22.5 kDa), the last one being subunit 6, which (like class b) functionally qualify as subunits of the membrane factor of the ATPase complex. As shown by labeling with 35SO24- and 3H-labeled amino acids, their biosynthesis is only very slightly cycloheximide-resistant, although it is submitted to coordinate regulation distinct from that of the class F1 peptides. 2. Consequently it was shown that the OLI2 gene product, a 20-kDa peptide with high cycloheximide-resistant label, which was generally taken to be 'subunit 6' of the ATPase, is not in fact identical to this peptide.

Adenosine Triphosphatases↗