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Biomedical subjects

D Weil

Publications and source records attributed to D Weil.

At least 19 recordsLinked to original sources
PubMed2006

Technical problems and complications of a transanal pull-through for Hirschsprung's disease.

BACKGROUND: The purpose of this study was to evaluate the technical difficulties and complications of a transanal pull-through for Hirschsprung's disease. MATERIAL AND METHODS: This report was based on a multicentric retrospective study of 65 cases. Pull-through procedures were transanal Swenson or Soave procedures in 26 and 39 cases, respectively. RESULTS: Evaluation of the aganglionic level, peri-rectal dissection, and anastomosis were the three steps in the procedure where surgeons encountered difficulties. Such difficulties led to serious complications in 3 cases. A patient with a colon biopsy before the pull-through procedure had a postoperative pneumoperitoneum requiring a second laparoscopy for suture and washing. Another patient had peritonitis due to anastomotic leakage. Finally, a difficult rectal dissection in a neonate led to a urethral injury requiring secondary urethral repair. Only 41 of the 65 patients had no abdominal scars (63 %). CONCLUSION: We considered the transanal pull-through for Hirschsprung's disease to be a reliable technique. Nevertheless, it requires an urethral stent, precise dissection, careful anastomosis and selected indications in order to avoid major complications.

Anastomosis, Surgical↗
PubMed2006

Targets for global tuberculosis control.

The United Nations Millennium Development Goals (MDGs) have added to the suite of targets and indicators used to evaluate progress in tuberculosis (TB) control. This paper reviews the history of target setting for TB control and lays out the complete set of indicators and targets that will guide TB control through to 2015, the target year for all MDGs.

Communicable Disease Control↗
PubMed2005

The translational regulator CPEB1 provides a link between dcp1 bodies and stress granules.

The cytoplasmic polyadenylation element-binding protein (CPEB) has been characterized in Xenopus laevis as a translational regulator. During the early development, it behaves first as an inhibitor and later as an activator of translation. In mammals, its closest homologue is CPEB1 for which two isoforms, short and long, have been described. Here we describe an additional isoform with a different RNA recognition motif, which is differentially expressed in the brain and ovary. We show that all CPEB1 isoforms are found associated with two previously described cytoplasmic structures, stress granules and dcp1 bodies. This association requires the RNA binding ability of the protein, whereas the Aurora A phosphorylation site is dispensable. Interestingly, the rck/p54 DEAD box protein, which is known as a CPEB partner in Xenopus and clam, and as a component of dcp1 bodies in mammals, is also present in stress granules. Both stress granules and dcp1 bodies are involved in mRNA storage and/or degradation, although so far no link has been made between the two, in terms of neither morphology nor protein content. Here we show that transient CPEB1 expression induces the assembly of stress granules, which in turn recruit dcp1 bodies. This dynamic connection between the two structures sheds new light on the compartmentalization of mRNA metabolism in the cytoplasm.

Alternative Splicing↗
PubMed2004

Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone.

AIM: To evaluate the efficacy of periocular triamcinolone acetonide for the treatment of thyroid associated ophthalmopathy (TAO), and the presence of ocular or systemic adverse effects. METHODS: A multicentre prospective pilot study was performed on patients diagnosed with Graves' ophthalmopathy less than 6 months before entry to the study. Patients were admitted to the study and were randomised into two groups: treatment and control. The treatment group received four doses of 20 mg of triamcinolone acetate 40 mg/ml in a peribulbar injection to the inferolateral orbital quadrant. Both groups were evaluated by measuring the area of binocular vision without diplopia on a Goldmann perimeter and the size of the extraocular muscles on computed tomography (CT) scans. Ophthalmological and systemic examinations were done to rule out ocular and systemic adverse effects. Follow up was 6 months for both groups. RESULTS: 50 patients were eligible for the study. 41 patients completed the study. There was an increase in the area of binocular vision without diplopia in the treatment group (Sigma initial: mean 231.1 (SD 99.9) and final absolute change, mean 107.1 (SD 129.0)) compared to the control group (Sigma initial: mean 350.7 (SD 86.5) and final absolute change, mean -4.5 (SD 67.6)). The sizes of the extraocular muscles were reduced in the treatment group (mean (inferior rectus initial values): 1.3 (0.7), final percentage change: -13.2 (25.7), medial rectus initial values: 1.2 (0.6), final percentage change: -8.2 (20.7), superior rectus-levator palpebrae initial values: 1.2 (0.6), final percentage change: -9.5 (29.1), lateral rectus initial values: 1.0 (0.4), final percentage change: -11.5 (20.6)) compared to the control group (inferior rectus initial values: 0.9 (0.3), final percentage change: -4.0 (21.5), medial rectus initial values: 0.9 (0.3), final percentage change: 0.6 (22.4), superior rectus-levator palpebrae initial values: 0.9 (0.3), final percentage change: 12.5 (37.5), lateral rectus initial values: 0.9 (0.4), final percentage change: -0.5 (31.6)). Both measurements (degree of diplopia and muscle thickness) were statistically significant between groups (initial - final). No systemic or ocular adverse effects were found. CONCLUSIONS: Triamcinolone administered as a periocular injection is effective in reducing diplopia and the sizes of extraocular muscles in TAO ophthalmopathy of recent onset. This form of treatment is not associated with systemic or ocular side effects.

Adult↗
PubMed2002

In vivo kinetics of mRNA splicing and transport in mammalian cells.

The kinetics of pre-mRNA processing in living cells is poorly known, preventing a detailed analysis of the regulation of these reactions. Using tetracycline-regulated promoters we performed, during a transcriptional induction, a complete analysis of the maturation of two cellular mRNAs, those for LT-alpha and beta-globin. In both cases, splicing was appropriately described by first-order reactions with corresponding half-lives ranging between 0.4 and 7.5 min, depending on the intron. Transport also behaved as a first-order reaction during the early phase of beta-globin expression, with a nuclear dwelling time of 4 min. At a later time, analysis was prevented by the progressive accumulation within the nucleus of mature mRNA not directly involved in export. Our results further establish for these genes that (i) splicing components are never limiting, even when expression is induced in naive cells, (ii) there is no significant RNA degradation during splicing and transport, and (iii) precursor-to-product ratios at steady state can be used for the determination of splicing rates. Finally, the comparison between the kinetics of splicing during transcriptional induction and during transcriptional shutoff reveals a novel coupling between transcription and splicing.

3T3 Cells↗
PubMed2002

Targeting the kinesin Eg5 to monitor siRNA transfection in mammalian cells.

RNA interference, the inhibition of gene expression by double-stranded RNA, provides a powerful tool for functional studies once the sequence of a gene is known. In most mammalian cells, only short molecules can be used because long ones induce the interferon pathway. With the identification of a proper target sequence, the penetration of the oligonucleotides constitutes the most serious limitation in the application of this technique. Here we show that a small interfering RNA (siRNA) targeting the mRNA of the kinesin Eg5 induces a rapid mitotic arrest and provides a convenient assay for the optimization of siRNA transfection. Thus, dose responses can be established for different transfection techniques, highlighting the great differences in response to transfection techniques of various cell types. We report that the calcium phosphate precipitation technique can be an efficient and cost-effective alternative to Oligofectamine in some adherent cells, while electroporation can be efficient for some cells growing in suspension such as hematopoietic cells and some adherent cells. Significantly, the optimal parameters for the electroporation of siRNA differ from those for plasmids, allowing the use of milder conditions that induce less cell toxicity. In summary, a single siRNA leading to an easily assayed phenotype can be used to monitor the transfection of siRNA into any type of proliferating cells of both human and murine origin.

Calcium Phosphates↗
PubMed2001

A specific promoter of the sensory cells of the inner ear defined by transgenesis.

To date, no promoter sequence specific to the inner ear sensory cells (hair cells) has been reported. In an effort to understand the molecular mechanisms that determine hair cell fate in the inner ear, and with the goal of developing a valuable tool for gene therapy and for the generation of conditional knockouts, we initiated a search for cis-acting DNA sequences that regulate the expression of the murine Myo7a and human MYO7A genes. These genes encode the unconventional myosin VIIA which is expressed in hair cells and in some other epithelial cells. We generated lines of transgenic mice expressing the green fluorescent protein (GFP ) reporter gene under the control of several 5'-truncated versions of the Myo7a/MYO7A promoter region and intron 1. We obtained transgenic mice with a GFP expression restricted to the hair cells of the inner ear, cochlea and vestibule. Successive deletions of the promoter allowed us to define a minimal sequence of 118 bp that is sufficient, in the presence of intron 1, to target the transgene expression to hair cells. In addition, the deletion of intron 1 from the transgenes abolished hair cell expression, thus indicating the presence of a strong enhancer in the intron. This is the first report of regulatory sequences sufficient to target the expression of a gene exclusively in sensory cells of the inner ear. It also opens up the possibility for the analysis of the hair cell transcriptome.

Animals↗
PubMed2001

Valuing the economic consequences of work injury and illness: a comparison of methods and findings.

BACKGROUND: Workplace injuries and fatalities in the US create significant economic costs to society. Although economic costs should measure the opportunity cost to society arising from injuries and fatalities, estimating them often proves difficult as a practical matter. This leads to a range of estimates for valuing these costs. METHODS: This paper compares methods of economic valuation, focusing in particular on how different methods diverge to varying degrees from measuring the "true" economic costs of injuries and illnesses. In so doing, it surveys the literature that has arisen in the past 25 years to measure different aspects of economic consequences. RESULTS: Estimates of the costs of injuries and fatalities tend to understate the true economic costs from a social welfare perspective, particularly in how they account for occupational fatalities and losses arising from work disabilities. CONCLUSION: Although data availability often makes estimation of social welfare costs difficult, researchers should attempt to more fully integrate such approaches into estimation procedures and interpretation of their results.

Accidents, Occupational↗
PubMed2001

Laparoscopic adrenalectomy in children.

BACKGROUND: The aim of this study was to describe the indications and results of laparoscopic adrenalectomy in children. METHODS: This retrospective multicenter study included six children (four boys, two girls) aged 2-16 years (mean, 9.5). Three children had hypertension. In three cases, the adrenal mass was discovered incidentally. The tumors were bilateral in two children, right-sided in two cases, and left-sided in two cases. The mean tumor size was 4 cm (range, 1-7). Each child underwent MIBG scintigraphy and MRI before the operation. RESULTS: Four right and two left adrenal glands were resected by laparoscopy (transperitoneal), and two left glands were resected by retroperitoneoscopy. Two conversions were necessary for two left adrenal glands (one retroperitoneoscopy, one laparoscopy). Two partial resections and six adrenalectomies were performed. Histological examination of the tumors revealed two ganglioneuromas, one neuroblastoma, and five pheochromocytomas (two bilateral). One child had an involved node (pheochromocytoma). Both bilateral pheochromocytomas had von Hippel-Lindau disease. There was no morbidity. Mean hospitalstay was 6 days. Postoperative evaluation at 1 month was normal in all children. CONCLUSION: The indications for laparoscopic adrenalectomy in children are benign tumors and pheochromocytomas. In these cases, laparoscopic adrenalectomy is feasible and safe, even in cases of pheochromocytoma.

Adolescent↗
PubMed2001

Diseases of the lacrimal drainage system.

We will refer to lacrimal system pathologies involving the outflow pathways, as well as to the recent advances in the management of canalicular and lacrimonasal duct anomalies, including modifications to dacrycystorhinostomy technique, treatment for congenital obstructions, and lacrimal intubations. Special emphasis will be placed on the usefulness of nasal and canalicular endoscopy for the examination and treatment of congenital obstructions and endonasal pathologies, as an aid for intubations and lacrimal surgery, as well as on reasons for failed procedures.

Humans↗
PubMed2001

Functional analysis of a dominant mutation of human connexin26 associated with nonsyndromic deafness.

Cx26 has been implicated in dominant (DFNA3) and recessive (DFNB1) forms of nonsyndromic sensorineural deafness. While most homozygous DFNB1 Cx26 mutations result in a simple loss of channel activity, it is less clear how heterozygous mutations in Cx26 linked to DFNA3 cause hearing loss. We have tested the ability of one dominant mutation (W44C) to interfere with wild-type human Cx26 (HCx26wt). HCx26wt induced robust electrical conductance between paired oocytes, and facilitated dye transfer between transfected HeLa cells. In contrast, oocyte pairs injected with only W44C were not electrically coupled above background levels, and W44C failed to dye couple transfected HeLa cells. Moreover, W44C dramatically inhibited intercellular conductance of HCx26wt when co-expressed in an equal ratio, and the low levels of residual conductance displayed altered gating properties. A nonfunctional recessive mutation (W77R) did not inhibit the ability of HCx26wt to form functional channels when co-injected in the same oocyte pairs, nor did it alter HCx26wt gating. These results provide evidence for a functional dominant negative effect of the W44C mutant on HCx26wt and explain how heterozygous Cx26 mutations could contribute to autosomal dominant deafness, by resulting in a net loss, and/or alteration, of Cx26 function.

Animals↗
PubMed2001

[Traumatic luxation of the globe into the maxilar sinus].

PURPOSE: We present a case of traumatic luxation of the ocular globe into the maxillary sinus. MATERIAL AND METHODS: Male patient, 23 years old with orbito-facial trauma and traumatic luxation of his right ocular globe into the maxillary sinus. CONCLUSION: To present an unusual case of traumatic prolapse of an undamaged ocular globe into a paranasal sinus.

Adult↗
PubMed2000

Mature mRNAs accumulated in the nucleus are neither the molecules in transit to the cytoplasm nor constitute a stockpile for gene expression.

In higher eukaryotes, the regulation of pre-mRNA processing is still poorly known. The accumulation of various mature mRNAs, which can be observed in the nuclei of mammalian cells, is suggestive of a regulatory role of transport. However, the significance of these nuclear mRNA is presently unknown. We have used a tetracycline-regulated promoter to investigate the dynamics of these pools of mRNAs upon arrest of transcription. We observed, for beta-globin and LT-alpha genes, a slow disappearance of these mRNA from the nucleus, with an apparent half-life that is similar to their cytoplasmic half-life. In view of these dynamics, these mRNA cannot simply be mature mRNAs in transit to the cytoplasm. They could be mRNAs retained in the nucleus, provided that the regulation of mRNA stability is comparable in the nucleus and the cytoplasm. But, because of their limited stability, these nuclear mRNAs cannot constitute a significant stock for gene expression. Alternatively, they could reflect a bidirectional transport of mRNA, that is, to and from the cytoplasm, which would provide a direct explanation for the similarity in both compartments of their half-life and poly(A) tail shortening over time.

3T3 Cells↗
PubMed2000

Internal drainage into an Onlay-Roux-en-Y jejunal loop in isolated pancreatic injury with ductal transection: short-term and long-term follow-up in two pediatric cases.

Two pediatric cases of isolated pancreatic injury treated by internal drainage into an Onlay-Roux-en-Y jejunal loop are reported. The discussion concerns the difficulties of early diagnosis, the importance of endoscopic retrograde cholangiopancreatography (ERCP) in surgery and the reasons for the choice of internal drainage by Onlay-Roux-en-Y jejunal loop in our two cases.

Abdominal Injuries↗
PubMed2000

DFNA3.

Explore the source record for details and available documents.

Chromosome Mapping↗
PubMed1999

Accumulation of mature mRNA in the nuclear fraction of mammalian cells.

Little is known about the nuclear mRNA content of mammalian cells. In this study, we analyzed by Northern blotting with a panel of probes the nuclear and cytoplasmic fractions derived from several rodent cell lines. For most of the genes under study, mature mRNAs could easily be detected in the nuclear fraction and accumulated to higher levels than the corresponding precursors. In addition, significant differences in the nucleo-cytoplasmic partition of mature mRNAs were observed between genes as well as between cell types (NIH 3T3, CTLL-2, D3-ES, PC-12), indicating that this nuclear accumulation of mRNA is regulated. Thus, while it is usually considered that splicing is the limiting step of pre-mRNA processing, these results point towards transport or nuclear retention of mRNA as a key determinant of nuclear mRNA metabolism.

Animals↗