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J Pucilowska

Publications and source records attributed to J Pucilowska.

9 recordsLinked to original sources
PubMed2005

A variant in the HS1-BP3 gene is associated with familial essential tremor.

BACKGROUND: Genetic linkage studies have identified two susceptibility loci for essential tremor (ET) on chromosomes 3q13 (ETM1) and 2p24.1 (ETM2). Linkage disequilibrium studies in separate population samples from the United States and Singapore suggest an association between ET and loci at ETM2. METHODS: Fine mapping studies were conducted on multiplex and singleton US families linked to ETM2 using newly detected loci within the candidate interval to establish the minimal critical region (MCR) harboring an ET gene. The genes and transcripts within this interval were systematically analyzed by single-strand conformational polymorphism analysis and DNA sequencing. RESULTS: A 464-kb region between loci D2S2150 and etm1231 was defined as the MCR. The coding regions and flanking intronic splice sites of two genes and seven transcripts in this interval were evaluated for mutations. A missense mutation (828C-->G) in the transcript FLJ14249 (HS1-BP3) was identified in one US family. This mutation was found in another apparently unrelated US family with ET and was absent in 150 control samples (300 chromosomes). The 828C-->G mutation causes a substitution of a glycine for an alanine residue in the HS1-BP3 protein. The HS1-BP3 protein binds to proteins that are highly expressed in motor neurons and Purkinje cells and regulate the Ca2+/calmodulin-dependent protein kinase activation of tyrosine and tryptophan hydroxylase. CONCLUSIONS: A rare variant in the HS1-BP3 gene that is associated with essential tremor (ET) in two families is reported. This finding will facilitate research on the functional role of this gene and related genes in the pathogenesis of ET.

Adult↗
PubMed2004

Candidate genes for recessive non-syndromic mental retardation on chromosome 3p (MRT2A).

A mild type of autosomal recessive, non-syndromic mental retardation (NSMR) is linked to loci on chromosome 3p. This report delimits the MRT2A minimal critical region to 4.2 Mb between loci D3S3630 and D3S1304. This interval contains nine genes (IL5RA, TRNT1, LRRN1, SETMAR, SUMF1, ITPR1, BHLHB2, EDEM, and MRPS36P1). The results suggest that a mutation does not exist in these genes and that an unknown transcript in the region contributes to the cognitive deficits in NSMR.

Chromosomes, Human, Pair 3↗
PubMed2004

Haplotype analysis at the ETM2 locus in a Singaporean sample with familial essential tremor.

An ancestral haplotype on chromosome 2p24.1 described in an American sample with familial essential tremor (ET) was analyzed in a different ethnic sample from Singapore. Six polymorphic loci (etm1240, etm1231, etm1234, APOB, etm1241, and etm1242) in a 274-kb interval within an ET gene candidate region (ETM2) were analyzed in Singaporean individuals with a family history of ET (n = 52) and compared to Singaporean controls older than age 65 (n = 49). The allele frequencies were significantly different between cases and controls for the loci etm1234 (p = 0.0001) and APOB (p = 0.0320). An extended haplotype formed by the loci etm1231, etm1234, and APOB occurred with a frequency of 31% in Singaporean cases and in 1.8% of elderly Singaporean controls (p = 0.0005). Haplotype studies in two different population samples suggest that a disease locus for ET lies near or within the 100-kb interval between the loci etm1231 and APOB.

Adolescent↗
PubMed2001

Hypothalamic-pituitary-adrenal axis function and corticosterone receptor expression in behaviourally characterized young and aged Long-Evans rats.

In the current investigation, hypothalamic-pituitary-adrenal (HPA) axis function was examined in young and aged male Long-Evans rats that were initially assessed on a version of the Morris water maze sensitive to cognitive impairment during ageing. In behaviourally characterized rats, a 1-h restraint stress paradigm revealed that plasma corticosterone concentrations in aged cognitively impaired rats took significantly longer to return to baseline following the stressor than did those in young or aged cognitively unimpaired rats. No differences in basal or peak plasma corticosterone concentrations, however, were observed between young or aged rats, irrespective of cognitive status. Using ribonuclease protection assays and in situ hybridization, we evaluated mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA abundance in young and aged rats characterized on the spatial task. Abundance of MR mRNA was decreased as a function of age in stratum granulosum but not hippocampus proper, and the decrease in MR mRNA was largely unrelated to cognitive status. However, GR mRNA was significantly reduced in several hippocampal subfields (i.e. stratum granulosum and temporal hippocampus proper) and other related cortical structures (medial prefrontal and olfactory regions) of aged cognitively impaired rats compared to either young or aged cognitively unimpaired cohorts, and was significantly correlated with spatial learning ability among the aged rats in each of these brain regions. In agreement with previous stereological data from this ageing model, no changes were detected in neuron density in the hippocampus of the rats used in the in situ hybridization analysis. These data are the first to describe a coordinated decrease in GR mRNA in a functional brain system including hippocampus and related cortical areas that occurs in tandem with impairments of the HPA response to stress and cognitive decline in ageing.

Adrenal Cortex Hormones↗
PubMed1999

Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts.

Normal luminal bacteria and bacterial cell wall polymers are implicated in the pathogenesis of chronic intestinal inflammation. To determine the direct involvement of bacteria and their products on intestinal fibrogenesis, the effects of purified bacterial cell wall polymers on collagen and cytokine synthesis were evaluated in intestinal myofibroblast cultures established from normal fetal and chronically inflamed cecal tissues. In this study, the intestines of Lewis rats were intramurally injected with peptidoglycan-polysaccharide polymers. Collagen and transforming growth factor (TGF)-beta1 mRNA levels were measured and correlated with mesenchymal cell accumulation by immunohistochemistry. The direct effects of cell wall polymers on fibrogenic cytokine and collagen alpha1 (type I) expression were evaluated in intestinal myofibroblast cultures. We found that intramural injections of bacterial cell wall polymers induced chronic granulomatous enterocolitis with markedly increased collagen synthesis and concomitant increased TGF-beta1 and interleukin (IL)-6 expression. Intestinal myofibroblast cultures were established, which both phenotypically and functionally resemble the mesenchymal cells that are involved in fibrosis in vivo. Bacterial cell wall polymers directly stimulated collagen alpha1 (I), TGF-beta1, IL-1beta, and IL-6 mRNA expression in the intestinal myofibroblasts derived from both normal and inflamed cecum. Neutralization of endogenous TGF-beta1 inhibited in vitro collagen gene expression. From our results, we conclude that increased exposure to luminal bacterial products can directly activate intestinal mesenchymal cells, which accumulate in areas of chronic intestinal inflammation, thus stimulating intestinal fibrosis in genetically susceptible hosts.

Animals↗
PubMed1992

Tissue-specific expression of insulin-like growth factor binding protein-3 protease activity during rat pregnancy.

The abundances of insulin-like growth factor binding proteins (IGFBPs) in sera and tissue homogenates of rats at days 12, 15, and 18 of pregnancy were determined by ligand- and immunoblotting. As in serum, IGFBP-3 was abundant in day 12 uterus, placenta, and fetuses, and decreased by day 15. On day 18 of pregnancy, IGFBP-2 was predominant and IGFBP-3 was less than 25% of day 12 values in fetus and placenta, and was undetectable in uterus and decidua. In contrast, IGFBPs in the nonreproductive tissues did not change significantly. IGFBP-3 was more abundant in muscle than heart and liver, and was not detected in lung, kidney, or brain. The decrease in IGFBP-3 in serum and reproductive tissues between days 12 and 15 of pregnancy was temporally related to the appearance of IGFBP-3 protease activity. Proteolytic activity was detectable only at low levels in brain, liver, and spleen, and was undetectable in lung, heart, muscle, and kidney. The specific protease inhibitors that blocked IGFBP-3 proteolytic activities in pregnant rat serum and decidua were virtually identical and suggested inhibition of a divalent cation-dependent tryptic-like serine protease. Furthermore, exposure of bovine IGFBP-3 (in nonpregnant bovine serum) or radiolabeled recombinant human IGFBP-3 to day 18 pregnant rat serum, decidua or uterus resulted in the generation of IGFBP-3 fragments with the same apparent Mrs (29-31 K and 18-23 K). We postulate that tissue-specific degradation may be as important as synthesis in determining IGFBP-3 abundance, and that the dramatic changes in IGFBPs in reproductive and fetal tissues may cause changes in IGF availability which are necessary for rapid tissue growth and differentiation.

Animals↗
PubMed1988

The circadian rhythm of melatonin in hypothyroidism and hyperthyroidism.

UNLABELLED: In order to determine the influence of thyroid function on the pineal gland in humans, the circadian rhythm of the serum melatonin concentration was estimated in 16 women with thyroid disorders: 8 with hypothyroidism and 8 with hyperthyroidism, as well as in 5 healthy controls. A significant melatonin circadian rhythm was observed in all the three groups studied. The melatonin rhythm parameters derived from cosinor analysis: mesor (controls: 0.163 +/- 0.03 nmol/l (+/- SEM), hypothyroid patients: 0.176 +/- 0.22 nmol/l, and hyperthyroid patients: 0.167 +/- 0.04 nmol), amplitude (0.155, 0.145 and 0.138 nmol/l, respectively), acrophase (1:38, 2:22 and 1:51 h, respectively) did not differ significantly in the three groups studied. Integrated 24-h melatonin secretion was also similar in patients and controls. The melatonin concentrations were positively correlated with TSH levels in hypothyroidism, and negatively correlated with T3 in hyperthyroidism. IN CONCLUSION: in patients with hypo- and hyperthyroidism the circadian rhythm of melatonin secretion is not altered.

Adult↗