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I Stec

Publications and source records attributed to I Stec.

15 recordsLinked to original sources
PubMed2006

Laser Doppler measurements of the vocal fold blood micro-circulation.

The authors have developed a laser Doppler method, referred to as LDF+LS (laser Doppler flowmetry by laryngostereometry), for measuring the vocal fold micro-circulation. The vocal folds of 103 patients were examined during general anesthesia. A laser Doppler probe was placed on defined positions at the vocal fold edge: midmembranous position (MP), 2 mm and 4 mm behind, and 1 mm anterior to MP. Three parameters were derived, ie, the concentration (CMBC) and velocity (V) of moving blood cells, and the product of both resulting in perfusion: P = CMBCxV. The results of 53 subjects with normal vocal fold status showed that the V at MP was significantly lower than 2 mm behind MP (P < 0.05). Men had significantly higher velocity than women (P < 0.05). Subjects older than 65 years had higher perfusion and CMBC as compared with younger subjects (P < 0.01). Smokers with normal vocal folds had higher velocity than non-smokers (P < 0.05). Measurements of healthy vocal folds were compared with benign vocal fold pathology. Vocal fold polyps had significantly higher perfusion than normal vocal folds (P < 0.01). In conclusion, the laser Doppler measurement is a sensitive tool estimating superficial blood flow in both normal and pathological vocal folds. The blood flow in normals differs with respect to gender and age probably due to variations in micro-circulation of the mucosa and lamina propria. Vocal fold pathology and external factors such as smoking result in blood flow changes.

Adult↗
PubMed2006

[Treatment of vitally endangered anorexia nervosa patients based on guardianship laws].

Anorexia nervosa is a psychiatric disorder occurring primarily in young women. Especially when chronic or the body mass index is less than 12 kg/m(2), it has a mortality of up to 20%. Often these patients are admitted to emergency units and treated internistically. If they accept psychiatric treatment, they are normally transferred to specialized psychosomatic units for further therapy. If patients are not able to accept necessary further therapy to overcome the danger to health and life, the question arises in terms of guardianship law of whether they are able to handle their personal concerns alone. After several vitally endangered anorexia nervosa patients had been admitted to our closed psychiatric ward, we developed a therapeutic concept for this subgroup of patients, taking the possibilities of guardianship law into account. This concept aims at restoring the body weight continuously and finally enable the patients to be transferred to less restrictive psychosomatic units. The chosen treatment is shown with the therapy courses of 25 patients treated according to this concept.

Adolescent↗
PubMed2001

WHSC1L1, on human chromosome 8p11.2, closely resembles WHSC1 and maps to a duplicated region shared with 4p16.3.

We have identified and characterized a gene (60% on protein level) and a pseudogene (93% on DNA level) that show high similarity to the Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1). These genes, WHSC1L1 and WHSC1L2P, map to human chromosomes 8p11.2 and 17q21, respectively. WHSC1L1 is ubiquitously expressed and, like WHSC1, generates two major transcripts, a short (s-type) and a long (l-type). The WHSC1L1 l-type transcript encodes a 1437-amino-acid protein containing 2 PWWP (proline-trypto-phan-proline-tryptophan) domains, 5 PHD (plant-home-domain)-type zinc finger motifs, a SAC (SET-associated Cys-rich) domain, and a SET (Suppressor of Variegation, Enhancer of Zeste and Trithorax) domain. The s-type transcript encodes a protein of 645 amino acids containing a PWWP domain only. WHSC1L2P is an unexpressed, intronless pseudogene of a WHSC1L1 s-type transcript. The 8p11.2 region around WHSC1L1 contains a set of genes including TACC1, FGFR1, LETM2, and WHSC1L1, which seems to be derived from a recent duplication involving 4p16.3 where a similar set of genes is located. Rearrangements of 8p are frequently found in human cancer, including breast cancer. These characteristics indicate that WHSC1L1 might have a role in embryonic development and, when disregulated, in cancer development.

Carrier Proteins↗
PubMed2001

A partial BRCA1 sequence homology mapping to 4q28.

Using a BRCA1 cDNA probe in Southern analysis, we detected a sequence of 348 bp on 4q28 that is homologous to the 3' end of BRCA1. A 28-kb sequence contig has been assembled spanning the homologous region, which we designated BRCA1-h. An open reading frame was identified encoding a sequence of 82 amino acids; 22 of the last 23 amino acids are identical to the last 23 residues of BRCA1. BLAST-searches, RT-PCR and RACE-experiments have been unable to provide evidence that BRCA1-h is part of an expressed gene.

Amino Acid Sequence↗
PubMed2000

The PWWP domain: a potential protein-protein interaction domain in nuclear proteins influencing differentiation?

Upon characterization of WHSC1, a gene mapping to the Wolf-Hirschhorn syndrome critical region and at its C-terminus similar to the Drosophila ASH1/trithorax group proteins, we identified a novel protein domain designated PWWP domain. To gain insight into its structure, evolutionary conservation and its potential functional role, we performed database searches to identify other PWWP domain-containing proteins. We retrieved 39 proteins, and a multiple alignment shows that the domain spans some 70 amino acids. It is present in proteins of nuclear origin and plays a role in cell growth and differentiation. Due to its position, the composition of amino acids close to the PWWP motif and the pattern of other domains present, we hypothesize that the domain is involved in protein-protein interactions.

Amino Acid Motifs↗
PubMed1998

WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.

Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known. We have identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously in early development and undergoes complex alternative splicing and differential polyadenylation. It encodes a 136 kDa protein containing four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain also found in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc finger. It is expressed preferentially in rapidly growing embryonic tissues, in a pattern corresponding to affected organs in WHS patients. The nature of the protein motifs, the expression pattern and its mapping to the critical region led us to propose WHSC1 as a good candidate gene to be responsible for many of the phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3) translocations recently described in multiple myelomas, at least three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.

Amino Acid Sequence↗
PubMed1997

Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p 16.3.

Recently, a deletion of chromosome 4pter was found in three patients with Pitt-Rogers-Danks syndrome. We investigated two of these patients, by means of DNA and FISH studies, together with two additional patients with Pitt-Rogers-Danks syndrome, to determine the critical region of the deletion in these patients and to compare this with the critical region in Wolf-Hirschhorn syndrome. All four patients showed terminal deletions of chromosome 4p of different sizes. One of them appeared to have an unbalanced karyotype caused by a cryptic translocation t(4;8) in the mother, resulting in a deletion of chromosome 4pter and a duplication of chromosome 8pter. The localisation of the Wolf-Hirschhorn critical region has been confined to approximately 1 Mb between D4S43 and D4S115. Our study shows that the deletions in four patients with the Pitt-Rogers-Danks syndrome overlap the Wolf-Hirschhorn critical region and extend beyond this in both directions. This study, combined with the fact that our third patient, who was previously described as a Pitt-Rogers-Danks patient, but who now more closely resembles a Wolf-Hirschhorn patient, makes it likely that Pitt-Rogers-Danks and Wolf-Hirschhorn syndromes are different clinical phenotypes resulting from a deletion in the same microscopic region on chromosome 4p16.

Abnormalities, Multiple↗
PubMed1996

Yeast artificial chromosome mapping of the cystinosis locus on chromosome 17p by fluorescence in situ hybridization.

The gene locus for cystinosis has been mapped between markers D17S1583 and D17S1584 on the short arm of chromosome 17. Using markers encompassing the cystinosis region, we assigned different yeast artificial chromosome (YAC) clones previously identified by sequence tagged site (STS) screening to 17p13.3. Three of the clones hybridized to the target 17p gene region; one of these was chimeric, hybridizing both to chromosomes 3p and 5q; two of the YACs did not contain sequences of 17p13.3. Our physical mapping has identified candidate YACs as a first step towards a positional cloning approach.

Amino Acid Sequence↗
PubMed1995

Long-term antidepressant treatment reduces behavioural deficits in transgenic mice with impaired glucocorticoid receptor function.

Impaired cognitive function and enhanced activity of the hypothalamic-pituitary-adrenocortical system are among the cardinal symptoms of major depression in humans that resolve after successful antidepressant treatment. We used a transgenic mouse model expressing antisense RNA complementary to that of glucocorticoid receptor (GR) mRNA to test the hypothesis that reduced GR function can cause these clinical disturbances. The transgenic mice show profound behavioural changes in a number of animal tests that are indicative of cognitive impairment. These mice also have elevated plasma corticotropin concentrations in response to stress. After long-term treatment with moclobemide, a reversible inhibitor of monoamine oxidase type A that acts clinically as an antidepressant, both the behavioural deficits and the hormonal alterations disappeared. These observations suggest that a transgenic mouse with GR dysfunction may be a useful model for investigation of drug effects on the cognitive and neuroendocrine aspects of depression.

Animals↗
PubMed1995

Estimate of severe autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D) among sporadic muscular dystrophy males: a study of 415 familes.

Ninety-five percent of cases of severe muscular dystrophy with early childhood onset result from mutations in the dystrophin region of the human X chromosome (DMD, McKusick 310200), whereas 5% are thought to result from mutations in autosomal genes. We examined a total of 415 families with at least one living patient whose clinical features suggested DMD. Based on formal genetics, haplotype analysis, and dystrophin determinations, we estimate that one in eight (11.8%) sporadic male patients carries autosomal rather than X chromosomal mutations.

Chromosome Aberrations↗
PubMed1994

Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats.

We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical (HPA) axis functioning when adult. To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge, 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10(8) human red blood cells (HRBC) or gram-negative bacterial endotoxin (Escherichia coli LPS: 30 micrograms/kg). The adult male progeny (3 mo old) of both experimental groups showed increased basal plasma corticosterone levels. In addition, after novelty stress the HRBC group, but not the LPS group, showed increased ACTH and corticosterone levels. Both groups showed substantial decreases in mineralocorticoid (MR) and glucocorticoid receptor (GR) levels in the hippocampus, a limbic brain structure critical for HPA axis regulation, whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased. HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti-HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes, respectively. This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood. Clinically, it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress.

Animals↗
PubMed1993

Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system.

The effects of the tricyclic antidepressant amitriptyline on the rat hypothalamic-pituitary-adrenocortical (HPA) system were studied. The time-course experiments showed that amitriptyline, given via the drinking water (4.5 mg/kg.day), produces significant decreases (P < 0.05) in adrenal weight after 5 (-20%) and 7 weeks (-21%) of treatment. Hippocampal mineralocorticoid receptor (MR) levels were down-regulated at days 3 (-27%) and 7 (-20%), and transiently up-regulated at 2 (+40%), 5 (+74%), and 7 (+18%) weeks of treatment. Hippocampal glucocorticoid receptor (GR) levels were slightly down-regulated at days 3 (-8%) and 7 (-17%), transiently up-regulated by 26% at 5 weeks, and indistinguishable from controls after 7 weeks of treatment. MR levels were unchanged in the hypothalamus and neocortex, whereas hypothalamic GR concentrations were elevated and neocortical receptor levels were not altered. Dose-response experiments showed significant decreases in adrenal weight when rats were treated with 4.5 (-14%), 8.8 (-16%) and 14.5 (-13%) mg/kg.day antidepressant, but this applied only for the 4.5- (-14%) and 8.8- (-12%) mg/kg.day doses when the ratio of adrenal weight to body weight was considered. The dose-response relationship regarding hippocampal GR content displayed an inverted U-shaped curve, whereas this was less marked for MR levels. A dose of 4.5 mg/kg.day appeared to be optimal for the rise in MR as well as GR. Concerning the neuroendocrine implications of chronic antidepressant treatment, amitriptyline (5 weeks, 4.5 mg/kg.day) produced significant decreases in basal (ACTH, -47%; corticosterone, -31%) as well as stress (30 min novel environment)-induced plasma ACTH (-38%) and corticosterone (-57%) levels. Previous experiments have forwarded a role of limbic MR in the tonic control of basal HPA activity. Based on the present data, we hypothesize that during amitriptyline treatment a rise in limbic MR may be the initial phenomenon in a successively adjusting HPA system, as evidenced by the decreasing plasma hormone concentrations, declining adrenal size, and up-regulation of GR in particular brain regions.

Adrenal Cortex↗
PubMedDate not supplied

Dexamethasone nonsuppression in transgenic mice expressing antisense RNA to the glucocorticoid receptor.

Transgenic mice with impaired glucocorticoid receptor (GR) function produced by partially knocking out GR gene expression with antisense RNA were treated with increasing dosages of dexamethasone. In these mice, ten-fold higher dexamethasone dosages were required to induce full suppression of plasma corticosterone than in normal mice. This relative dexamethasone insensitivity adds to the evidence that these transgenic mice could serve as an appropriate model to study the negative feedback disturbance of the hypothalamic-pituitary-adrenocortical system in affective disorders.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Nephropathic cystinosis (CTNS-LSB): construction of a YAC contig comprising the refined critical region on chromosome 17p13.

A yeast artificial chromosome (YAC) contig was constructed encompassing the entire region on chromosome 17p13 where the autosomal recessive disorder infantile nephropathic cystinosis (MIM 21980, CTNS-LSB) has been genetically mapped. It comprises seven clones ordered by their content of a series of six sequence-tagged sites (STSs). Fluorescence in situ hybridisation (FISH) revealed two chimaeric clones. The order of four polymorphic STSs mapped with the contig was consistent with that of the known genetic map with the exception of markers D17S1583 (AFMb307zg5) and D17S1798 (AFMa202xf5) where a telomeric location of D17S1583 was inferred from the contig; two non-polymorphic STSs were localised within the marker frame-work. From the analysis of recombination events in an unaffected individual as defined by leucocyte cystine levels we support the high-resolution mapping of this region to a small genetic interval and show that it is entirely represented on a single, non-chimaeric YAC clone in the contig.

Chromosome Mapping↗