PubMed Health⌕ Search

Biomedical subjects

V Janssens

Publications and source records attributed to V Janssens.

18 recordsLinked to original sources
PubMed2002

Observation of a supernumerary hamstring muscle: a state of the art on its incidence and clinical relevance.

During routine anatomic dissection of the lower extremities of a 67-year-old male body, a supernumerary ishiocrural muscle was observed. This supernumerary muscle had similarities to a rare variant of the semimembranous muscle. On the left side it arose from the lateral dorsal side of the femur between the short head of the biceps femoris muscle and the origin of the adductor magnus muscle. It inserted on the medial condyle deep to the normal insertion of the semimembranous at the posterior aspect of the articular capsule. This muscle can be regarded either as a short deep semimembranous muscle (M. semimembranosus profondus) or as a short belly of a semitendinous biceps as known in birds. The muscle was situated closely to the vessels and nerves of the popliteal region. On the right side a similar but somewhat fainter muscle was observed whose origin emanated from the fascia of the adductor magnus muscle. The muscle probably has no major clinical importance but might be important to the surgeon who has to intervene in the popliteal region.

Aged↗
PubMed2001

Inhibition of the Wnt signaling pathway by the PR61 subunit of protein phosphatase 2A.

Axin, a negative regulator of the Wnt signaling pathway, forms a complex with glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, adenomatous polyposis coli (APC) gene product, and Dvl, and it regulates GSK-3beta-dependent phosphorylation in the complex and the stability of beta-catenin. Using yeast two-hybrid screening, we found that regulatory subunits of protein phosphatase 2A, PR61beta and -gamma, interact with Axin. PR61beta or -gamma formed a complex with Axin in intact cells, and their interaction was direct. The binding site of PR61beta on Axin was different from those of GSK-3beta, beta-catenin, APC, and Dvl. Although PR61beta did not affect the stability of beta-catenin, it inhibited Dvl- and beta-catenin-dependent T cell factor activation in mammalian cells. Moreover, it suppressed beta-catenin-induced axis formation and expression of siamois, a Wnt target gene, in Xenopus embryos, suggesting that PR61beta acts either at the level of beta-catenin or downstream of it. Taken together with the previous observations that PR61 interacts with APC and functions upstream of beta-catenin, these results demonstrate that PR61 regulates the Wnt signaling pathway at various steps.

Animals↗
PubMed2001

The Saccharomyces cerevisiae phosphotyrosyl phosphatase activator proteins are required for a subset of the functions disrupted by protein phosphatase 2A mutations.

In Saccharomyces cerevisiae, PTPA is encoded by two genes, YPA1 and YPA2. In order to examine the biological role of PTPA as potential regulator of protein phosphatase 2A (PP2A), we compared the phenotypes of the ypaDelta mutants with these of PP2A-deficient strains. While deletion of both YPA genes is lethal, deletion of YPA1 alone results in a phenotype resembling that of PP2A-deficient strains in specific aspects such as aberrant bud morphology, abnormal actin distribution, and similar growth defects under various growth conditions. These phenotypes were even more pronounced when YPA1 was deleted in a pph21Delta genetic background. Moreover, ypaDelta mutants are hypersensitive to nocodazole and show inappropriate mitotic spindle formation as previously described for mutants in the catalytic subunit of PP2A, suggesting that Ypa, like PP2A, has a function in mitotic spindle formation. These results are consistent with an in vivo role of Ypa as a regulator of PP2A. However, unlike a PP2A-deficient strain, ypaDelta mutants do not show a G2 arrest. Therefore, Ypa does not seem to play a role in the regulation of PP2A at this stage of the cell cycle. These results imply that Ypa regulates a specific subset of PP2A functions, possibly by controlling the subunit composition of PP2A.

Actins↗
PubMed2001

Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.

Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon.

Animals↗
PubMed2000

The Saccharomyces cerevisiae homologue YPA1 of the mammalian phosphotyrosyl phosphatase activator of protein phosphatase 2A controls progression through the G1 phase of the yeast cell cycle.

The Saccharomyces cerevisiae gene YPA1 encodes a protein homologous to the phosphotyrosyl phosphatase activator, PTPA, of the mammalian protein phosphatase type 2A (PP2A). In order to examine the biological role of PTPA, we disrupted YPA1 and characterised the phenotype of the ypa1Delta mutant. Comparison of the growth rate of the wild-type strain and the ypa1Delta mutant on glucose-rich medium after nutrient depletion showed that the ypa1Delta mutant traversed the lag period more rapidly. This accelerated progression through "Start" was also observed after release from alpha-factor-induced G1 arrest as evidenced by a higher number of budding cells, a faster increase in CLN2 mRNA expression and a more rapid reactivation of Cdc28 kinase activity. This phenotype was specific for deletion of YPA1 since it was not observed when YPA2, the second PTPA gene in budding yeast was deleted. Reintroduction of YPA1 or the human PTPA cDNA in the ypa1Delta mutant suppressed this phenotype as opposed to overexpression of YPA2. Disruption of both YPA genes is lethal, since sporulation of heterozygous diploids resulted in at most three viable spores, none of them with a ypa1Delta ypa2Delta genotype. This observation indicates that YPA1 and YPA2 share some essential functions. We compared the ypa1Delta mutant phenotype with a PP2A double deletion mutant and a PP2A temperature-sensitive mutant. The PP2A-deficient yeast strain also showed accelerated progression through the G1 phase. In addition, both PP2A and ypa1Delta mutants show similar aberrant bud morphology. This would support the notion that YPA1 may act as a positive regulator of PP2A in vivo.

CDC28 Protein Kinase, S cerevisiae↗
PubMed2000

The phosphotyrosyl phosphatase activator gene is a novel p53 target gene.

The minimal promoter of the phosphotyrosyl phosphatase activator (PTPA) gene, encoding a regulator of protein phosphatase 2A contains two yin-yang 1 (YY1)-binding sites, positively regulating promoter activity. We now describe a role for p53 in the regulation of PTPA expression. Luciferase reporter assays in Saos-2 cells revealed that p53 could down-regulate PTPA promoter activity in a dose-dependent manner, whereas four different p53 mutants could not. The p53-responsive region mapped to the minimal promoter. Overexpression of YY1 reverses the repressive effect of p53, suggesting a functional antagonism between p53 and YY1. The latter does not involve competition for YY1 binding, but rather direct control of YY1 function. Inhibition of PTPA expression by endogenous p53 was demonstrated in UVB-irradiated HepG2 cells, both on the mRNA and protein level. Also basal PTPA levels are higher in p53-negative (Saos-2) versus p53-positive (HepG2, U2OS) cells, suggesting "latent" p53 can control PTPA expression as well. The higher PTPA levels in U2OS cells, programmed to overexpress constitutively a dominant-negative p53 mutant, corroborate this finding. Thus, PTPA expression is negatively regulated by p53 in normal conditions and in conditions where p53 is up-regulated, via an as yet unknown mechanism involving the negative control of YY1.

Binding Sites↗
PubMed2000

Identification and characterization of alternative splice products encoded by the human phosphotyrosyl phosphatase activator gene.

The phosphotyrosyl phosphatase activator (PTPA), a protein phosphatase 2A (PP2A) regulatory protein, specifically stimulates the phosphotyrosyl phosphatase activity of PP2A in vitro. Human PTPA is encoded by a single gene, the structure and chromosomal localization of which have been determined in our previous work. In this paper, we report the identification and characterization of six additional splice variants, termed PTPAbeta to PTPAeta, in addition to the originally identified PTPAalpha form. Interestingly, PTPAbeta and PTPAgamma contain a novel exon that had been overlooked in the formerly identified gene structure. As revealed by nested PCR, all these PTPA transcripts are expressed in various human cDNA libraries and cell lines. However, a quantitative approach, using a single PCR reaction followed by detection of the reaction products with a radioactively labeled probe, revealed only PTPAalpha, beta and delta, suggesting that the other transcripts are expressed very poorly. In vitro transcription-translation revealed that only PTPAalpha, beta, delta and epsilon are translated into functional proteins, whereas translation of PTPAgamma, zeta and eta is stopped prematurely due to a frameshift resulting from skipping exon 2, suggesting that the latter isoforms may result from splicing errors. By western analysis of HepG2 and Saos-2 cell extracts, only PTPAalpha and beta were detected. PTPAalpha and beta were expressed as GST fusion proteins in bacteria, and were found to contain the same specific phosphotyrosyl phosphatase stimulatory activity towards PP2A. The identification of this family of PTPA variants adds another level of complexity to the in vivo function(s) of PTPA, opening up the possibility that different isoforms may perform different functions.

Alternative Splicing↗
PubMed1999

Functional analysis of the promoter region of the human phosphotyrosine phosphatase activator gene: Yin Yang 1 is essential for core promoter activity.

The phosphotyrosine phosphatase activator (PTPA) has been isolated as an in vitro regulator of protein phosphatase 2A. Human PTPA is encoded by a single gene, the structure and chromosomal localization of which have been determined in our previous work. Here we describe the further isolation, sequencing and functional characterization of the PTPA promoter region. In agreement with its ubiquitous expression, the PTPA promoter displays several characteristics of housekeeping genes: it lacks both a TATA-box and a CAAT-box, it is very GC-rich and it contains an unmethylated CpG island surrounding the transcription initiation site. Transient transfection experiments in different cell types with several truncated chimaeric luciferase reporter gene plasmids revealed the importance of the region between positions -67 and -39 for basal promoter activity. This region coincides remarkably well with the determined CpG island. Further analysis of this region demonstrated the presence of a Yin Yang 1 (YY1) binding motif at positions -52 to -44. Binding of YY1 to this sequence is demonstrated in bandshift and DNase I footprinting experiments. Another YY1 binding motif is found in the 5' untranslated region, at positions +27 to +35. Mutations in either of these sites, abolishing YY1 binding in vitro, have differential effects on promoter activity. Point mutations in both sites completely abolish promoter activity. Moreover, induction of promoter activity by co-transfection with a YY1 expression plasmid is fully dependent upon the presence of both intact YY1 binding sites. Thus YY1 apparently mediates basal transcription of the human PTPA gene through two binding sites within its proximal promoter.

Animals↗
PubMed1999

Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue.

The carboxyl methyltransferase, which is claimed to exclusively methylate the carboxyl group of the C-terminal leucine residue of the catalytic subunit of protein phosphatase 2A (Leu(309)), was purified from porcine brain. On the basis of tryptic peptides, the cDNA encoding the human homologue was cloned. The cDNA of this gene encodes for a protein of 334 amino acids with a calculated M(r) of 38 305 and a predicted pI of 5.72. Database screening reveals the presence of this protein in diverse phyla. Sequence analysis shows that the novel methyltransferase is distinct from other known protein methyltransferases, sharing only sequence motifs supposedly involved in the binding of adenosylmethionine. The recombinant protein expressed in bacteria is soluble and the biophysical, catalytic, and immunological properties are indistinguishable from the native enzyme. The methylation of PP2A by the recombinant protein is restricted to Leu(309) of PP2A(C). No direct effects on phosphatase activity changes were observed upon methylation of the dimeric or trimeric forms of PP2A.

Amino Acid Sequence↗
PubMed1998

Functional analysis of conserved domains in the phosphotyrosyl phosphatase activator. Molecular cloning of the homologues from Drosophila melanogaster and Saccharomyces cerevisiae.

Phosphotyrosyl phosphatase activator (PTPA), a 37 kDa cytosolic protein that specifically activates the phosphotyrosyl phosphatase activity of the dimeric form of PP2A, was cloned from Drosophila melanogaster and Saccharomyces cerevisiae. Sequence alignment of PTPA from yeast to human revealed highly conserved regions including the type B fragment of the putative PTPA ATP binding site. We generated PTPA deletion mutants of these conserved regions as well as point mutations within regions that were suggested to be functionally important. The recombinant proteins were expressed in E. coli and subsequently purified. Activity measurements, linked with immunological detection, revealed that most of the well-conserved regions are essential for PTPA activity. However, neither the type A fragment of the putative ATP binding site nor the cysteine-rich region, present in all but the Drosophila and yeast homologues, appeared to be essential for PTPA activity. Moreover, we observed that PTPA truncated at glycine266 behaves as a dominant negative mutant since it is inhibitory to the wild-type PTPA.

Adenosine Triphosphate↗
PubMed1995

Protein contact dermatitis: myth or reality?

Protein contact dermatitis is a dermatosis which usually presents as a chronic eczema with episodic acute exacerbations a few minutes after contact with the offending allergen. Patch tests with the responsible allergen are usually negative, and the diagnosis can only be made by means of scratch or prick tests with the allergen. Sometimes, specific IgE antibodies can be detected in the blood. As there is considerable confusion about this entity, we have reviewed the cases reported in the literature.

Dermatitis, Contact↗
PubMed1994

Post-mortem limitations of body composition analysis by computed tomography.

Few of the indirect methods for measuring body composition have every been validated against direct human cadaver evidence. Computed tomography (CT), like NMR, has proved to be an important diagnostic tool and they appear to be the techniques of the future for body composition studies. The purpose of the present study (Cadaver Analysis Study III), undertaken at the Vrije Universiteit Brussel in a joint venture with the University of Göteborg, Sweden, was to validate tomographic measurements of volumes and areas from different tissues using data from CT-scanning of unembalmed deep-frozen cadavers and data collected by dissection of the same cadavers. Six Belgian adults were extensively measured and dissected. The body was divided into several slices for comparison of the CT image with photography of the same slice and comparison of tissue-volumes per segment for the whole body. Due to post-mortem changes and the frozen state of the cadavers, the CT measurements were greatly affected by artefacts disturbing adipose tissue (AT) and muscle area determinations. Only the bone area measurements were similar between the two techniques. However, when the volumes (per segment) of the same tissues were considered, no apparent difference was found between CT and dissection data for the muscle volume.

Aged↗
PubMed1993

alpha-Amylase, a flour additive: an important cause of protein contact dermatitis in bakers.

BACKGROUND: alpha-Amylase, an enzyme commonly used in flour additives, has been reported to be an important cause of rhinitis and asthma in bakers. OBJECTIVE: Our purpose was to determine whether this enzyme could also cause dermatitis. We tested it routinely in bakers with hand eczema. METHODS: Patch tests were administered with the International Contact Dermatitis Research Group standard series and a bakery series and scratch-chamber or prick tests were performed with the bakers' own material and with alpha-amylase powder. RESULTS: Of 32 bakers tested, seven had an immediate wheal-and-flare reaction and two also had a delayed eczematous reaction. High dilutions of the alpha-amylase powder still gave strong reactions. CONCLUSION: alpha-Amylase is an important cause of skin reactions in bakers and should be tested routinely if a contact allergy is suspected.

Adult↗
PubMedDate not supplied

Relationships between visceral, trunk and whole-body adipose tissue weights by cadaver dissection.

BACKGROUND: Despite the important association of central adiposity and cardiovascular and other risk factors, there are only three reported values for directly weighed visceral adipose tissue (AT). All other reported values are based on medical imaging techniques. OBJECTIVE: The study aimed to investigate the relationships between visceral, trunk and total AT weights in older men and women. METHODS: Data was obtained from the combination of two studies involving the complete dissection of 15 male and 16 female cadavers (age range 55-94 years) and allowed for compartmentation into skin, AT, muscle, bone and a residual component, divided over six body segments: head, trunk, legs and arms. Visceral AT was separated from trunk subcutaneous AT. All tissues were weighed. RESULTS: Visceral AT weights ranged from 0.3 to 5.8 kg. Mean values were 3.00 +/- 1.52 kg (mean +/- SE) for the men and 3.24 +/- 1.67 kg for the women. These were not significantly different (p = 0.68), but visceral AT weight, expressed as a percentage of total body AT weight was significantly greater (p = 0.02) in the men (16.8 +/- 5.4%) than in the women (12.9 +/- 3.5%). Correlations between visceral AT weight and the weight of subcutaneous AT of the trunk were highly significant (men, r = 0.70, women, r = 0.81, p < 0.005), with similar slopes for the two sexes. The correlation coefficients of visceral with total body AT weights were even greater (men, r = 0.83 and women, r = 0.96, p < 0.0001). CONCLUSIONS: In this sample of older Belgians, visceral AT is strongly related to total body adiposity, corresponding to an increment of about 200 g of visceral AT for every kilogram of total AT in men and about 180 g in women. Because of this relationship, techniques such as skinfold calipers and ultrasound for assessing whole body fatness from measurement of only the subcutaneous layer are thus able to account for visceral adiposity.

Adipose Tissue↗
PubMedDate not supplied

Database-supported teleconferencing: an additional clinical mentoring tool to assist a multinational company HIV/AIDS treatment program in Africa.

BACKGROUND: The lack of human resources for health is presently recognized as a major factor limiting scale-up of antiretroviral treatment (ART) programs in resourcelimited settings. The mobilization of public and private partners, the decentralization of care, and the training of non-HIV specialist nurses and general practitioners could help increase the number of HIV-infected patients receiving ART. In addition to other forms of training, scheduled teleconferences (TCs) have been organized to support a comprehensive HIV treatment program delivered by a private company's health team. OBJECTIVE: To describe the role of the TC as an additional tool in mentoring a company's health care workers (HCWs). METHOD: For this study, all TC reports were retrospectively reviewed and the questions classified by topic. Participating Heineken physicians evaluated the technical quality and scientific relevance of the TCs through an anonymous survey. RESULTS: From October 2001 to December 2003, 10 HCWs working in 14 operating companies in 5 African countries raised 268 problems during 45 TCs. A total of 79 questions (29%) were asked about antiretroviral (ARV) therapy, 53 (20%) about the diagnosis and treatment of opportunistic infection, 43 (16%) about ARV toxicity, 40 (15%) about care organization and policy, 32 (12%) about laboratory or drug supply, and 21 (8%) about biological parameters. The mean TC attendance rate was 70%. The level of satisfaction among local company physicians was 65% for logistics, 89% for scientific relevance, 84% for applicability of advice, and 85% overall. The most common complaints concerned the poor quality of the telephone connection and language problems for francophone participants. CONCLUSION: Database-supported teleconferencing could be an additional tool to mentor company HCWs in their routine care of HIV-infected workers and family members. The role and costeffectiveness of telemedicine in improving health outcomes should be further studied.

Africa↗