PubMed Health⌕ Search

Biomedical subjects

P Groenen

Publications and source records attributed to P Groenen.

16 recordsLinked to original sources
PubMed2006

Steroid and G protein binding characteristics of the seatrout and human progestin membrane receptor alpha subtypes and their evolutionary origins.

A novel progestin receptor (mPR) with seven-transmembrane domains was recently discovered in spotted seatrout and homologous genes were identified in other vertebrates. We show that cDNAs for the mPR alpha subtypes from spotted seatrout (st-mPRalpha) and humans (hu-mPRalpha) encode progestin receptors that display many functional characteristics of G protein-coupled receptors. Flow cytometry and immunocytochemical staining of whole MDA-MB-231 cells stably transfected with the mPRalphas using antibodies directed against their N-terminal regions show the receptors are localized on the plasma membrane and suggest the N-terminal domain is extracellular. Both recombinant st-mPRalpha and hu-mPRalpha display high affinity (Kd 4.2-7.8 nm), limited capacity (Bmax 0.03-0.32 nm), and displaceable membrane binding specific for progestins. Progestins activate a pertussis toxin-sensitive inhibitory G protein (G(i)) to down-regulate membrane-bound adenylyl cyclase activity in both st-mPRalpha- and hu-mPRalpha-transfected cells. Coimmunoprecipitation experiments demonstrate the receptors are directly coupled to the G(i) protein. Similar to G protein-coupled receptors, dissociation of the receptor/G protein complex results in a decrease in ligand binding to the mPRalphas and mutation of the C-terminal, and third intracellular loop of st-mPRalpha causes loss of ligand-dependent G protein activation. Phylogenetic analysis indicates the mPRs are members of a progesterone and adipoQ receptor (PAQR) subfamily that is only present in chordates, whereas other PAQRs also occur in invertebrates and plants. Progesterone and adipoQ receptors are related to the hemolysin3 family and have origins in the Eubacteria. Thus, mPRs arose from Eubacteria independently from members of the GPCR superfamily, which arose from Archeabacteria, suggesting convergent evolution of seven-transmembrane hormone receptors coupled to G proteins.

Animals↗
PubMed2001

Recurrent involvement of chromosomal region 6q21 in heterotaxy.

We present a patient with heterotaxy and a de novo, apparently balanced reciprocal translocation with breakpoints at 6q21 and 20p13. Another patient with heterotaxy was previously reported with a de novo balanced translocation involving chromosome band 6q21. The breakpoints in both patients on 6q21 were found to be located in the same chromosomal region spanning maximally 2 Mb. We speculate that the two breakpoints lead to the disruption of the function of a single gene, either directly or through long distance effects. Alternatively, the present observation suggests additional heterogeneity in heterotaxy in humans.

Abnormalities, Multiple↗
PubMed2001

Comparative study of ASCA (Anti-Saccharomyces cerevisiae antibody) assays in inflammatory bowel disease.

BACKGROUND & AIMS: Anti-Saccharomyces cerevisiae antibody (ASCA) is a serologic marker associated with Crohn's disease (CD). Although there is still discussion on its clinical value, several companies each promote their own ASCA assay to be used in the gastroenterologist's practice at considerable expense. The aim of this study was to determine whether different ASCA assays agree sufficiently well for the results to be used interchangeably. METHODS: Blood obtained from a large cohort of IBD patients with inflammatory bowel disease (IBD; 100 with CD, 100 with ulcerative colitis [UC]) and 178 controls (100 healthy blood donors and 78 patients with non-IBD diarrheal illnesses) was studied with 4 different ASCA assays. Sensitivity, specificity, and positive predictive value were compared. Agreement between assays was evaluated. RESULTS: Sensitivity of ASCA for CD ranged between 41% and 76%. Sensitivity was inversely related to specificity and positive predictive value. Results correlated well overall (range = 0.54-0.90) and the different ROC curves showed good agreement. When recalculated cutoff points were used, interchangeability increased. However, large differences were seen when absolute values were compared. CONCLUSIONS: A large range in sensitivities and specificities of ASCA for CD is seen with different ASCA assays, mainly as a consequence of the cutoff value chosen for each individual assay. Although agreement between and within assays is good, caution is important when absolute values are used. Standardization of ASCA measurements is greatly needed.

Adolescent↗
PubMed2000

NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry.

NIPP1 is a regulatory subunit of a species of protein phosphatase-1 (PP1) that co-localizes with splicing factors in nuclear speckles. We report that the N-terminal third of NIPP1 largely consists of a Forkhead-associated (FHA) protein interaction domain, a known phosphopeptide interaction module. A yeast two-hybrid screening revealed an interaction between this domain and a human homolog (CDC5L) of the fission yeast protein cdc5, which is required for G(2)/M progression and pre-mRNA splicing. CDC5L and NIPP1 co-localized in nuclear speckles in COS-1 cells. Furthermore, an interaction between CDC5L, NIPP1, and PP1 in rat liver nuclear extracts could be demonstrated by co-immunoprecipitation and/or co-purification experiments. The binding of the FHA domain of NIPP1 to CDC5L was dependent on the phosphorylation of CDC5L, e.g. by cyclin E-Cdk2. When expressed in COS-1 or HeLa cells, the FHA domain of NIPP1 did not affect the number of cells in the G(2)/M transition. However, the FHA domain blocked beta-globin pre-mRNA splicing in nuclear extracts. A mutation in the FHA domain that abolished its interaction with CDC5L also canceled its anti-splicing effects. We suggest that NIPP1 either targets CDC5L or an associated protein for dephosphorylation by PP1 or serves as an anchor for both PP1 and CDC5L.

Amino Acid Sequence↗
PubMed2000

GATA3 haplo-insufficiency causes human HDR syndrome.

Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal malformations. Studies in patients with 10p deletions have defined two non-overlapping regions that contribute to this complex phenotype. These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the region for the hypoparathyroidism, sensorineural deafness, renal anomaly (HDR) syndrome (Mendelian Inheritance in Man number 146255), which is located more telomeric (10p14-10pter). We have performed deletion-mapping studies in two HDR patients, and here we define a critical 200-kilobase region which contains the GATA3 gene. This gene belongs to a family of zinc-finger transcription factors that are involved in vertebrate embryonic development. Investigation for GATA3 mutations in three other HDR probands identified one nonsense mutation and two intragenic deletions that predicted a loss of function, as confirmed by absence of DNA binding by the mutant GATA3 protein. These results show that GATA3 is essential in the embryonic development of the parathyroids, auditory system and kidneys, and indicate that other GATA family members may be involved in the aetiology of human malformations.

Amino Acid Sequence↗
PubMed1999

Partial DiGeorge syndrome in two patients with a 10p rearrangement.

We describe 2 patients with a partial DiGeorge syndrome (facial dysmorphism, hypoparathyroidism, renal agenesis, mental retardation) and a rearrangement of chromosome 10p. The first patient carries a complex chromosomal rearrangement, with a reciprocal insertional translocation between the short arm of chromosome 10 and the long arm of chromosome 8, with karyotype 46, XY ins(8;10) (8pter 8q13::10p15-->10p14::8q24.1-->8qter) ins(10:8) (10pter--> 10p15::8q24.1-->8q13::10p14-->10qter). The karyotype of the second patient shows a terminal deletion of the short arm of chromosome 10. In both patients, the breakpoints on chromosome 10p reside outside the previously determined DiGeorge critical region II (DGCRII). This is in agreement with previous reports of patients with a terminal deletion of 10p with breakpoints distal to the DGCRII and renal malformations/hypoparathyroidism, and thus adds to evidence that these features may be caused by haploinsufficiency of one or more genes distal to the DGCRII.

Child↗
PubMed1999

The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome.

We reviewed 36 patients with a deletion of the short arm of chromosome 10 and a partial DiGeorge syndrome. We compared the phenotypes observed in these del(10p) patients with the classical DiGeorge phenotype associated with del(22q11), pointing out both similarities and differences. Some features, such as sensorineural hearing loss, seem to be highly associated with a deletion of 10p but are absent in the classical DiGeorge spectrum caused by del(22q11).

Abnormalities, Multiple↗
PubMed1998

Expanding complexity in myotonic dystrophy.

Myotonic dystrophy (DM) is a highly variable multisystemic disease belonging to the rather special class of trinucleotide expansion disorders. DM results from dynamic expansion of a perfect (CTG)n repeat situated in a gene-dense region on chromosome 19q. Based on findings in patient materials or cellular and animal models, many mechanisms for the causes and consequences of repeat expansion have been proposed; however, none of them has enjoyed prolonged support. There is now circumstantial evidence that long (CTG)n repeats may affect the expression of any of at least three genes, myotonic dystrophy protein kinase (DMPK), DMR-N9 (gene 59), and a DM-associated homeodomain protein (DMAHP). Furthermore, the new findings suggest that DM is not a simple gene-dosage or gain-or-loss-of-function disorder but that entirely new pathological pathways at the DNA, RNA, or protein level may play a role in its manifestation.

Animals↗
PubMed1998

Vesico-ureteral reflux: a genetic condition?

Vesico-ureteral reflux (VUR) is a frequent condition, but in most instances, the precise cause is unknown. We here review the evidence of a genetic aetiology of VUR, inherited as an autosomal dominant trait, with variable expression. We discuss the possible pathogenetic relationship between VUR and other types of uropathies and possible strategies towards the identification of genes underlying VUR are presented. The isolation of the gene(s) responsible for uropathies will not only lead to a better insight into the embryology of the urological system, the pathogenesis of uropathies, but also to a renewed interest from clinicians in congenital uropathies.

Child↗
PubMed1998

Can event-related potentials be evoked by extra-cochlear stimulation and used for selection purposes in cochlear implantation?

To investigate whether electrically evoked event-related responses (P300) could be elicited by extra-cochlear stimulation, measurements were performed on a group of adults fitted with the single-channel extra-cochlear implant. To optimize measurement conditions, and because of the low number of subjects still using an extra-cochlear device in our cochlear implant programme, measurements were also performed on a group of experienced users fitted with the intra-cochlear Nucleus multichannel device. For reference purposes, subjects with normal hearing (control group) were also included in the study. Reproducible late latency responses (N1 and P2 peaks) were found in the five extra-cochlear implant users, while P300s were present in four out of these five subjects. The latencies were longer than those of the control group, but were similar to those obtained in the intra-cochlear implant group. Significant correlations were found for most N1, P2 and P300 measurements evoked by the tonal stimuli and by speech stimuli. The P300 amplitudes, evoked by either tonal or speech stimuli, appeared to be related to speech perception ability. This led to the conclusion that N1, P2 and P300 measurements may have potential as a clinical tool for preoperative prediction and postoperative evaluation of sound processing on a cortical level.

Adolescent↗
PubMed1996

Perception of voicing cues by children with early otitis media with and without language impairment.

Research on the relationship between early otitis media with effusion (OME), language impairment, and central auditory processing has been equivocal. Identification and discrimination tasks provide us with a sensitive method of assessing speech perception on both an auditory and a phonetic level. The present study examined identification and discrimination of initial bilabial stop consonants differing in voicing by 9-year-old children with a history of severe OME. The groups studied were controlled for language impairment. The ability of these children to perceive major and minor voicing cues was examined using multiple voicing cues. Long-term effects of OME were found for both identification and discrimination performance. Children with OME produced an overall inconsistency in categorization, which suggests poorer phonetic processing. Discrimination was measured by means of "just noticeable differences" (JND). Children with early OME experience demonstrated a greater mean JND than children without early OME experience. Finally, in cases of language impairment with early OME, there was no additional deterioration of auditory or phonetic processing. It appears that either early OME or language impairment can lead to poorer perception.

Adult↗
PubMed1996

The specific relation between perception and production errors for place of articulation in developmental apraxia of speech.

Developmental apraxia of speech is a disorder of phonological and articulatory output processes. However, it has been suggested that perceptual deficits may contribute to the disorder. Identification and discrimination tasks offer a fine-grained assessment of central auditory and phonetic functions. Seventeen children with developmental apraxia (mean age 8:9, years:months) and 16 control children (mean age 8:0) were administered tests of identification and discrimination of resynthesized and synthesized monosyllabic words differing in place-of-articulation of the initial voiced stop consonants. The resynthetic and synthetic words differed in the intensity of the third formant, a variable potentially enlarging their clinical value. The results of the identification task showed equal slopes for both subject groups, which indicates no phonetic processing deficit in developmental apraxia of speech. The hypothesized effect of the manipulation of the intensity of the third formant of the stimuli was not substantiated. However, the children with apraxia demonstrated poorer discrimination than the control children, which suggests affected auditory processing. Furthermore, analyses of discrimination performance and articulation data per apraxic subject demonstrated a specific relation between the degree to which auditory processing is affected and the frequency of place-of-articulation substitutions in production. This indicates the interdependence of perception and production. The results also suggest that the use of perceptual tasks has significant clinical value.

Apraxias↗
PubMedDate not supplied

On the clinical relevance of mismatch negativity: results from subjects with normal hearing and cochlear implant users.

Mismatch negativity (MMN) provides an objective measure for evaluating subjects with problems related to speech processing. For a valid neurophysiological profile of speech-processing mechanisms, an efficient procedure to elicit MMNs is needed. In Experiment 1 of this study, MMN recordings were conducted in adults with normal hearing on the effects of decreasing the duration of the interstimulus interval (ISI). Shortening ISI duration does not seem to have a high impact on the individual MMN quality, whereas it does influence group MMN quality. In Experiment 2, MMNs were elicited in a group of cochlear implant users by using a speech sound contrast/ba/-/da/. A group of good performers produced a significant MMN, whereas a group of moderate performers did not. There seems to be a relation between speech perception ability and MMN quality. To fundamentally understand the effects of electrical stimulation of the inner ear and to clinically adjust rehabilitation, diverse data are needed on different aspects of auditory processing. Optimizing the procedure to elicit and MMN is therefore of great clinical value.

Adult↗
PubMedDate not supplied

Electrically evoked auditory middle latency responses versus perception abilities in cochlear implant users.

Electrical auditory middle latency responses (EAMLRs) were recorded in a group of 12 postlingually and 4 congenitally deaf cochlear implant users. The EAMLRs of the postlingually deaf cochlear implant users were compared to behavioral measures of speech perception. All the cochlear implant users showed pronounced EAMLR morphology and amplitude. EAMLRs of congenitally deaf cochlear implant users were remarkably similar to those of postlingually deaf cochlear implant users. The difference in speech perception ability between congenitally deaf and postlingually deaf cochlear implant users did not seem to be caused by integrity differences of the neural generators of the auditory middle latency response. For the postlingually deaf subjects, EAMLR amplitude variation and interlatency variation seemed to be related to specific aspects of speech perception. The poorer performers demonstrated more diversity in the amplitude of the EAMLR component peaks and a more diffuse EAMLR peak latency organization across the electrodes than the better performers.

Adolescent↗