Biomedical subjects

J Pintar

Publications and source records attributed to J Pintar.

11 recordsLinked to original sources

PubMed2006

Combined cytosine arabinoside and prednisone therapy for meningoencephalitis of unknown aetiology in 10 dogs.

OBJECTIVES: The differential diagnosis for young to middle-aged dogs with progressive neurological signs, focal or multifocal computed tomography/magnetic resonance imaging lesions, mononuclear cerebrospinal fluid pleocytosis and negative infectious titres includes granulomatous meningoencephalomyelitis, breed-specific meningoencephalitis, infectious meningoencephalitis of unknown origin and central nervous system neoplasia. The terminology meningoencephalitis of unknown aetiology may be preferable for cases that lack histopathological diagnoses. The safety and efficacy of a combination of cytosine arabinoside and prednisone protocol is evaluated, in this study, for the treatment of meningoencephalitis of unknown aetiology in 10 dogs. METHODS: Cases were selected based on neuroanatomical localisation, negative regional infectious disease titres, cerebrospinal fluid pleocytosis and brain imaging. Clinical response was gauged through follow-up examinations, owner and referring veterinarian surveys and review of medical records. RESULTS: Partial or complete remission was achieved in all dogs; the median survival time for the 10 dogs was 531 days (range 46 to 1025 days), with five of the 10 dogs alive at the time of writing. CLINICAL SIGNIFICANCE: Prednisone/cytosine arabinoside is a safe empirical therapy for dogs with meningoencephalitis of unknown aetiology; this drug combination may prolong survival time.

Animals↗

PubMed2001

Quantitative autoradiographic mapping of the ORL1, mu-, delta- and kappa-receptors in the brains of knockout mice lacking the ORL1 receptor gene.

Until recently the opioid receptor family was thought to consist of only the mu-, delta- and kappa-receptors. The cloning of opioid receptor like receptor (ORL1) and its endogenous ligand nociceptin/orphanin FQ, which displayed anti-opioid properties, has raised the issue of functional co-operativity of this system with the classical opioid system. ORL1 receptor knockout mice have been successfully developed by homologous recombination to allow the issue of potential heterogeneity of this receptor and also of compensatory changes in mu-, delta- or kappa-receptors in the absence of ORL1 to be addressed. We have carried out quantitative autoradiographic mapping of these receptors in the brains of mice that are wild-type, heterozygous and homozygous for the deletion of the ORL1 receptor. ORL1, mu-, delta- and kappa-receptors were labelled with [(3)H] leucyl-nociceptin (0.4 nM), [(3)H] DAMGO (4 nM), [(3)H] deltorphin-I (7 nM), and [(3)H] CI-977 (2.5 nM) respectively. An approximately 50% decrease in [(3)H] leucyl-nociceptin binding was seen in heterozygous ORL1 mutant mice and there was a complete absence of binding in homozygous brains indicating the single gene encodes for the ORL1 receptor and any putative subtypes. No significant gross changes in the binding to other opioid receptors were seen across genotypes in the ORL1 mutant mice demonstrating a lack of major compensation of classical opioid receptors in the absence of ORL1. There were a small number of region specific changes in the expression of classical opioid receptors that may relate to interdependent function with ORL1.

Analgesics, Opioid↗

PubMed2001

Female preproenkephalin-knockout mice display altered emotional responses.

The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear + shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark-light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001-20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety.

Animals↗

PubMed2001

OMNI scale perceived exertion at ventilatory breakpoint in children: response normalized.

PURPOSE: The Children's OMNI Scale of Perceived Exertion was used to identify a response normalized rating of perceived exertion (RPE)-Overall, RPE-Legs, and RPE-Chest that corresponds to the ventilatory breakpoint (Vpt) in 8- to 12-yr-old female and male children. METHODS: Subjects were a priori stratified into two fitness groups on the basis of peak oxygen uptake (VO2 peak): average (A) (41.0-49.0 mL x kg(-1) x min(-1); N = 24) and above average (AA) (50.0-58.0 mL x kg(-1) x min(-1); N = 24). Vpt was determined by a progressive cycle ergometer protocol to VO2 peak. RESULTS: A gender effect was not observed for any descriptive or dependent variable. Mean VO2peak for the A group was 1.72 L x min(-1) and for the AA group 2.04 L x min(-1). Vpt corresponded to 64.0% VO2 peak for A and 74.0% VO2peak for AA. RPE-Overall (mean A and AA, 6.1), RPE-Legs (mean A and AA, 7.2), and RPE-Chest (mean A and AA, 4.5) did not differ between the fitness groups. CONCLUSION: Findings indicated that undifferentiated and differentiated RPE-Vpt were similar between female and male children who varied in VO2peak and Vpt. A comparatively stable RPE-Vpt for 8- to 12-yr-old children that vary in VO2peak and Vpt indicates a group normalized perceptual response.

Anaerobic Threshold↗

PubMed1999

Subcellular localization of mannose 6-phosphate glycoproteins in rat brain.

The intracellular transport of soluble lysosomal enzymes relies on the post-translational modification of N-linked oligosaccharides to generate mannose 6-phosphate (Man 6-P) residues. In most cell types the Man 6-P signal is rapidly removed after targeting of the precursor proteins from the Golgi to lysosomes via interactions with Man 6-phosphate receptors. However, in brain, the steady state proportion of lysosomal enzymes containing Man 6-P is considerably higher than in other tissues. As a first step toward understanding the mechanism and biological significance of this observation, we analyzed the subcellular localization of the rat brain Man 6-P glycoproteins by combining biochemical and morphological approaches. The brain Man 6-P glycoproteins are predominantly localized in neuronal lysosomes with no evidence for a steady state localization in nonlysosomal or prelysosomal compartments. This contrasts with the clear endosome-like localization of the low steady state proportion of mannose-6-phosphorylated lysosomal enzymes in liver. It therefore seems likely that the observed high percentage of phosphorylated species in brain is a consequence of the accumulation of lysosomal enzymes in a neuronal lysosome that does not fully dephosphorylate the Man 6-P moieties.

Animals↗

PubMed1990

Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis.

The mouse insulin-like growth factor II (IGF-II) gene encodes a polypeptide that plays a role in embryonic growth. We have examined the temporal and spatial pattern of expression of this gene in sections of the mouse conceptus between embryonic days 4.0 and 8.5 by in situ hybridization. Abundant IGF-II transcripts were detected in all the trophectodermal derivatives, after implantation. Labeling was then observed in primitive endoderm, but was transient and disappeared after formation of the yolk sac. Expression was next detected in extraembryonic mesoderm at the early primitive streak stage. Labeling in the embryo proper appeared first at the late primitive streak/neural plate stage in lateral mesoderm and in anterior-proximal cells located between the visceral endoderm and the most cranial region of the embryonic ectoderm. The position of the latter cells suggests that their descendants are likely to participate in the formation of the heart and the epithelium of the ventral and lateral walls of the foregut, where intense labeling was observed at the neural fold stage. Hybridization was also detected in cranial mesenchyme, including neural crest cells. The intensity of hybridization signal increased progressively in paraxial (presomitic and somitic) mesoderm, while declining in the ectoplacental cone. The neuroectoderm and surface ectoderm did not exhibit hybridization at any stage. Immunohistochemical analysis indicated co-localization of IGF-II transcripts, translated pre-pro-IGF-II, and the cognate IGF-II/mannose-6-phosphate receptor. These correlations are consistent with the hypothesis that IGF-II has an autocrine function.

Animals↗

PubMed1989

Induction of the TRPM-2 gene in cells undergoing programmed death.

RNA and protein products encoded by the testosterone-repressed prostate message-2 gene (TRPM-2) are induced to high levels, coordinate with the onset of cell death, in numerous rodent models of inducible tissue damage. These models include cell death initiated by hormonal stimuli (prostate regression), pressure insult (renal atrophy after ureteral obstruction), developmental stimuli (necrosis of interdigital tissue), and cytotoxic injury (chemotherapeutic regression of a tumor). Sequence analysis of cDNA encoding TRPM-2 revealed its close homology with a product referred to as SGP-2 or clusterin expressed constitutively by Sertoli cells; however, the immunologically related polypeptides expressed in regressing tissues differ in molecular mass from the forms secreted by the testis. Although the function(s) of the products encoded by the TRPM-2 gene remains unclear, their presence provides a remarkable and early indicator of programmed cell death in many types of mammalian cells.

Animals↗

PubMed1988

Pattern of the insulin-like growth factor II gene expression during rat embryogenesis.

The rat insulin-like growth factor II (IGF-II) gene, encoding a fetal somatomedin, expresses a family of transcripts in embryonic/fetal tissues, and also in the adult choroid plexus and the leptomeninges. We have localized IGF-II gene transcripts in sections of rat embryos of embryonic days 10-16 by performing in situ hybridization. These transcripts are present in the head mesenchyme, formed from both the mesoderm and the cephalic portion of the neural crest, and also in the majority of other tissues of mesodermal origin, predominantly those derived from the somites and the lateral mesoderm. Intense labelling was detected in muscle cells, and their precursors, throughout the examined stages, whereas in chondrocytes the initial high level of hybridization declined substantially prior to ossification. IGF-II gene transcripts are also present in derivatives of other germ layers, but in restricted sites. Thus, from the derivatives of the endoderm, only the liver and the bronchial epithelium yielded hybridization signals. Ectoderm-derived tissues, including the central and peripheral nervous system, were negative for hybridization, with the exception of the choroid plexus, the newly forming pituitary rudiment and, to a lesser extent, the auditory placode. The pattern of IGF-II gene expression during embryogenesis overlaps significantly with the reported distribution of immunohistochemically detected TGF-beta 1. A paracrine/autocrine role for IGF-II in the developmental process is discussed.

Animals↗

PubMed1987

Tissue-specific and developmentally regulated transcription of the insulin-like growth factor 2 gene.

Transcription of the rat and human IGF-2 gene loci is unusually complex. The pattern of expression of these genes varies both between tissues and within a given tissue during different stages of development. Alternative splicing or possibly transcriptional initiation events generate variant IGF-2 mRNAs that contain different 5'-untranslated leader sequences. These leader exon sequences are shared with non-IGF-2 mRNAs. Certain noncoding IGF-2 gene sequence elements are transcribed extensively and are found in multiple copies elsewhere in the human genome. Furthermore, IGF-2 mRNA levels are particularly high in a variety of human malignancies.

Age Factors↗

PubMed1987

Susceptibility testing of macrolide antibiotics against Haemophilus influenzae and correlation of in vitro results with in vivo efficacy in a mouse septicemia model.

There is poor correlation between the MICs and zone sizes obtained for erythromycin against Haemophilus influenzae. The effect of two media, Mueller-Hinton medium supplemented with 3% lysed horse blood and 10 micrograms of NAD per ml (MHA + LYHB) and Mueller-Hinton agar supplemented with 1% bovine hemoglobin and 1% IsoVitaleX (MHA + HGB), on the MICs and zone sizes of erythromycin against H. influenzae was determined. The effect of three different methods for inoculum preparation on the susceptibility of H. influenzae was also determined. The MICs were independent of the method of inoculum preparation, but the zone sizes were smaller if the inoculum was carefully adjusted to contain approximately 10(8) CFU/ml. MICs were higher and zone sizes were smaller when MHA + HGB was used instead of MHA + LYHB. Good correlation was found when MHA + LYHB was used for determining the MIC and MHA + HGB was used for determining susceptibility by the disk method. When the inoculum was adjusted to match a McFarland 0.5 standard, the viable counts had to be approximately 10(8) CFU/ml for good correlation between MICs and zone sizes. A-56268, a new macrolide antibiotic, was tested against H. influenzae, and its MICs and tentative breakpoints against this organism were determined. The MICs obtained by various methods were correlated with in vivo efficacy by using a mouse septicemia model. MICs obtained on MHA + HGB or MHA + LYHB incubated without a 5% CO2 atmosphere showed the best correlation with in vivo efficacy.

Animals↗

PubMed1982

A screening test for assessing iron status.

Intervention strategies to combat iron deficiency anemia in developing countries may hasten the development of iron overload in patients with an inherited defect in hemoglobin synthesis. This risk could be diminished if there was a rapid and simple method available for detecting iron overload in population screening programs. We have developed such a method, which is in effect a semiquantitative ferritin measurement based on a modification of a two-site enzyme-linked immunoassay. The assay requires only 2 drops of whole blood and a total incubation time of 90 min. The procedure, which can readily distinguish iron deficiency from even a modest increase in storage iron, has a potentially wide application in settings where a prompt assessment of iron status is required.

Anemia, Hypochromic↗